|
1
|
Wang C, Wei F, Sun X, Qiu W, Yu Y, Sun D, Zhi Y, Li J, Fan Z, Lv G, Wang G. Exploring potential predictive biomarkers through historical perspectives on the evolution of systemic therapies into the emergence of neoadjuvant therapy for the treatment of hepatocellular carcinoma. Front Oncol 2024; 14:1429919. [PMID: 38993637 PMCID: PMC11236692 DOI: 10.3389/fonc.2024.1429919] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Accepted: 06/13/2024] [Indexed: 07/13/2024] Open
Abstract
Hepatocellular carcinoma (HCC), a type of liver cancer, ranks as the sixth most prevalent cancer globally and represents the third leading cause of cancer-related deaths. Approximately half of HCC patients miss the opportunity for curative treatment and are then limited to undergoing systemic therapies. Currently, systemic therapy has entered the era of immunotherapy, particularly with the advent of immune-checkpoint inhibitors (ICIs), which have significantly enhanced outcomes for patients with advanced HCC. Neoadjuvant treatment for HCC has become a possibility-findings from the IMbrave 050 trial indicated that ICIs offer the benefit of recurrence-free survival for high-risk HCC patients post-resection or local ablation. However, only a small fraction of individuals benefit from systemic therapy. Consequently, there is an urgent need to identify predictive biomarkers for treatment response and outcome assessment. This study reviewed the historical progression of systemic therapy for HCC, highlighting notable therapeutic advancements. This study examined the development of systemic therapies involving conventional drugs and clinical trials utilized in HCC treatment, as well as potential predictive biomarkers for advanced and/or locally advanced HCC. Various studies have revealed potential biomarkers in the context of HCC treatment. These include the association of dendritic cells (DCs) with a favorable response to neoadjuvant therapy, the presence of enriched T effector cells and tertiary lymphoid structures, the identification of CD138+ plasma cells, and distinct spatial arrangements of B cells in close proximity to T cells among responders with locally advanced HCC receiving neoadjuvant cabozantinib and nivolumab treatment. Furthermore, pathological response has been associated with intratumoral cellular triads consisting of progenitor CD8+ T cells and CXCL13+ CD4+ T helper cells surrounding mature DCs in patients receiving neoadjuvant cemiplimab for resectable HCC. Despite no widely recognized predictive biomarkers for HCC individualized treatment, we believe neoadjuvant trials hold the most promise in identifying and validating them. This is because they can collect multiple samples from resectable HCC patients across stages, especially with multi-omics, bridging preclinical and clinical gaps.
Collapse
Affiliation(s)
- Chuanlei Wang
- Department of Hepatobiliary and Pancreatic Surgery I, General Surgery Center, The First Hospital of Jilin University, Changchun, China
- Key Laboratory of the General Surgery Health Department of Jilin Province, Changchun, China
| | - Feng Wei
- Department of Hepatobiliary and Pancreatic Surgery I, General Surgery Center, The First Hospital of Jilin University, Changchun, China
- Key Laboratory of the General Surgery Health Department of Jilin Province, Changchun, China
| | - Xiaodong Sun
- Department of Hepatobiliary and Pancreatic Surgery I, General Surgery Center, The First Hospital of Jilin University, Changchun, China
- Key Laboratory of the General Surgery Health Department of Jilin Province, Changchun, China
| | - Wei Qiu
- Department of Hepatobiliary and Pancreatic Surgery I, General Surgery Center, The First Hospital of Jilin University, Changchun, China
- Key Laboratory of the General Surgery Health Department of Jilin Province, Changchun, China
| | - Ying Yu
- Department of Hepatobiliary and Pancreatic Surgery I, General Surgery Center, The First Hospital of Jilin University, Changchun, China
| | - Dawei Sun
- Department of Hepatobiliary and Pancreatic Surgery I, General Surgery Center, The First Hospital of Jilin University, Changchun, China
- Key Laboratory of the General Surgery Health Department of Jilin Province, Changchun, China
| | - Yao Zhi
- Department of Hepatobiliary and Pancreatic Surgery I, General Surgery Center, The First Hospital of Jilin University, Changchun, China
- Key Laboratory of the General Surgery Health Department of Jilin Province, Changchun, China
| | - Jing Li
- Department of Hepatobiliary and Pancreatic Surgery I, General Surgery Center, The First Hospital of Jilin University, Changchun, China
| | - Zhongqi Fan
- Department of Hepatobiliary and Pancreatic Surgery I, General Surgery Center, The First Hospital of Jilin University, Changchun, China
- Key Laboratory of the General Surgery Health Department of Jilin Province, Changchun, China
| | - Guoyue Lv
- Department of Hepatobiliary and Pancreatic Surgery I, General Surgery Center, The First Hospital of Jilin University, Changchun, China
- Key Laboratory of the General Surgery Health Department of Jilin Province, Changchun, China
| | - Guangyi Wang
- Department of Hepatobiliary and Pancreatic Surgery I, General Surgery Center, The First Hospital of Jilin University, Changchun, China
- Key Laboratory of the General Surgery Health Department of Jilin Province, Changchun, China
| |
Collapse
|
|
2
|
Ningarhari M, Bertez M, Ploquin A, Bertrand N, Desauw C, Cattan S, Catala P, Vandamme H, Cheymol C, Truant S, Lassailly G, Louvet A, Mathurin P, Dharancy S, Turpin A. Conventional cytotoxic chemotherapy for gastrointestinal cancer in patients with cirrhosis: A multicentre case-control study. Liver Int 2024; 44:682-690. [PMID: 38031969 DOI: 10.1111/liv.15813] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2023] [Revised: 11/08/2023] [Accepted: 11/23/2023] [Indexed: 12/01/2023]
Abstract
BACKGROUND & AIMS Progresses in management make a higher proportion of cirrhotic patients with gastrointestinal (GI) cancer candidates to chemotherapy. Data are needed on the safety and liver-related events associated with the use of chemotherapy in these patients. METHODS Forty-nine patients with cirrhosis receiving chemotherapy against GI cancer from 2013 to 2018 were identified in the French Health Insurance Database using ICD-10 codes K70-K74, and matched 1:2 to non-cirrhotic controls (n = 98) on age, tumour type and type of treatment. Adverse events (AE), dose tapering, discontinuation rate, liver-related events and survival rate were compared. RESULTS Patients with cirrhosis (Child-Pugh A 91%) more often received lower doses (38.8% vs 7.1%, p < .001), without significant differences in terms of grade 3/4 AE or dose tapering rates (29.6% vs. 36.7%; 22.3% vs 24.4%, respectively). Treatment discontinuation rate was higher in patients with cirrhosis (23.3% vs. 11.3%, p = .005). Child-Pugh (p = .007) and MELD (p = .025) scores increased under chemotherapy. Five patients with cirrhosis (10.2%) had liver decompensation within 12 months, and 17.2% of deaths in the cirrhosis group were liver-related versus 0% in matched controls. WHO-PS stage > 1 (HR 3.74, CI95%: 2.13-6.57, p < .001), TNM-stage M1 (HR 3.61, CI 95%: 1.82-7.16, p < .001), non-colorectal cancer (HR 1.73, CI 95%: 1.05-2.86, p = .032) and bilirubin higher than 5 mg/dL (HR 2.26, CI 95%: 1.39-3.70, p < .001) were independent prognostic factors of 2-year mortality, whereas cirrhosis was not. CONCLUSIONS Chemotherapy should be proposed only in patients with compensated cirrhosis with close monitoring of liver function. Dose management remains challenging. Multidisciplinary management is warranted to improve these patients' outcomes.
Collapse
Affiliation(s)
- Massih Ningarhari
- CHU Lille, Hôpital Huriez, Maladies de l'Appareil Digestif, Lille, France
| | - Marlène Bertez
- CHU Lille, Hôpital Huriez, Maladies de l'Appareil Digestif, Lille, France
| | - Anne Ploquin
- Université de Lille, CNRS INSERM UMR9020-U1277, CANTHER Cancer Heterogeneity Plasticity and Resistance to Therapies, Lille, France
- CHU Lille, Hôpital Huriez, Medical Oncology Department, Lille, France
| | - Nicolas Bertrand
- Université de Lille, CNRS INSERM UMR9020-U1277, CANTHER Cancer Heterogeneity Plasticity and Resistance to Therapies, Lille, France
- CHU Lille, Hôpital Huriez, Medical Oncology Department, Lille, France
| | - Christophe Desauw
- Université de Lille, CNRS INSERM UMR9020-U1277, CANTHER Cancer Heterogeneity Plasticity and Resistance to Therapies, Lille, France
- CHU Lille, Hôpital Huriez, Medical Oncology Department, Lille, France
| | - Stéphane Cattan
- CHU Lille, Hôpital Huriez, Maladies de l'Appareil Digestif, Lille, France
| | - Pascale Catala
- Centre Hospitalier de Béthune, Hépato-Gastro-Entérologie, Beuvry, France
| | - Hélène Vandamme
- Centre Hospitalier de Béthune, Hépato-Gastro-Entérologie, Beuvry, France
| | - Claire Cheymol
- GHICL Hôpital Saint-Vincent, Oncologie Médicale, Lille, France
| | - Stéphanie Truant
- CHU Lille, Hôpital Huriez, Chirurgie Digestive et Transplantation, Lille, France
| | | | - Alexandre Louvet
- CHU Lille, Hôpital Huriez, Maladies de l'Appareil Digestif, Lille, France
| | - Philippe Mathurin
- CHU Lille, Hôpital Huriez, Maladies de l'Appareil Digestif, Lille, France
| | - Sébastien Dharancy
- CHU Lille, Hôpital Huriez, Maladies de l'Appareil Digestif, Lille, France
| | - Anthony Turpin
- Université de Lille, CNRS INSERM UMR9020-U1277, CANTHER Cancer Heterogeneity Plasticity and Resistance to Therapies, Lille, France
- CHU Lille, Hôpital Huriez, Medical Oncology Department, Lille, France
| |
Collapse
|
|
3
|
Chen YH, Tsai CH, Chen YY, Wang CC, Wang JH, Hung CH, Kuo YH. Real-world comparison of pembrolizumab and nivolumab in advanced hepatocellular carcinoma. BMC Cancer 2023; 23:810. [PMID: 37644388 PMCID: PMC10463359 DOI: 10.1186/s12885-023-11298-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2023] [Accepted: 08/13/2023] [Indexed: 08/31/2023] Open
Abstract
BACKGROUND Nivolumab and pembrolizumab have not been directly compared in clinical trials, and the aim of this study is to investigate the efficacy and safety of nivolumab versus pembrolizumab in patients with advanced hepatocellular carcinoma (HCC) in real-world practice. METHODS We retrospectively reviewed patients with HCC who received intravenous nivolumab or pembrolizumab alone as second-line and later therapy. The objective response was determined according to the Response Evaluation Criteria in Solid Tumors criteria version 1.1. Adverse events (AEs) were graded based on the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. The Kaplan-Meier method was used to analyze progression-free survival (PFS) and overall survival (OS). Prognostic values were estimated using hazard ratios with 95% confidence intervals (CIs). RESULTS In total, 120 patients were enrolled, including 95 who received nivolumab and 25 who received pembrolizumab. All patients were staged as Barcelona Clinic Liver Cancer stage C, and 29 patients were classified as Child-Pugh classification B (7). The response rate of the pembrolizumab and nivolumab groups were 8.0% and 7.4%, respectively. There was no significant difference in the median PFS between the pembrolizumab and nivolumab groups (2.7 months versus 2.9 months). The median OS in the nivolumab group was longer than that in the pembrolizumab group (10.8 months versus 8.1 months); however, the difference was not statistically significant. The effects of pembrolizumab and nivolumab on the median PFS and OS were consistent across the subgroups based on baseline characteristics. The severity of all AEs was grades 1-2 without treatment interruption or dose adjustment; there was no statistically significant difference in the incidence of treatment-related AEs between these two groups. Additionally, the percentage of patients receiving subsequent therapy was consistent between the two groups. CONCLUSION The efficacy and safety of pembrolizumab and nivolumab were comparable in the management of patients with pretreated HCC in real-world practice.
Collapse
Affiliation(s)
- Yen-Hao Chen
- Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, No.123, Dapi Rd., Niaosong Dist, 833, Kaohsiung, Taiwan.
- School of Medicine, College of Medicine, Chang Gung University, 333, Taoyuan, Taiwan.
- School of Medicine, Chung Shan Medical University, 402, Taichung, Taiwan.
- Department of nursing, School of nursing, Fooyin University, 831, Kaohsiung, Taiwan.
| | - Ching-Hua Tsai
- Division of Trauma Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 833, Kaohsiung, Taiwan
| | - Yen-Yang Chen
- Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, No.123, Dapi Rd., Niaosong Dist, 833, Kaohsiung, Taiwan
| | - Chih-Chi Wang
- Division of General Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 833, Kaohsiung, Taiwan
| | - Jing-Houng Wang
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 833, Kaohsiung, Taiwan
| | - Chao-Hung Hung
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 833, Kaohsiung, Taiwan
| | - Yuan-Hung Kuo
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 833, Kaohsiung, Taiwan
| |
Collapse
|
|
4
|
Oranratnachai S, Rattanasiri S, Sirachainan E, Tansawet A, Raunroadroong N, McKay GJ, Attia J, Thakkinstian A. Treatment outcomes of advanced hepatocellular carcinoma in real-life practice: Chemotherapy versus multikinase inhibitors. Cancer Med 2022; 12:3046-3053. [PMID: 36082831 PMCID: PMC9939209 DOI: 10.1002/cam4.5224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Revised: 07/24/2022] [Accepted: 08/23/2022] [Indexed: 11/09/2022] Open
Abstract
BACKGROUND Multikinase inhibitors (MKIs) represent the main treatment options for advanced hepatocellular carcinoma (aHCC). However, accessibility in developing countries is limited. A chemotherapy, Fluorouracil and Oxaliplatin (FOLFOX), offers a less expensive treatment. Therefore, this study sought to compare the clinical effectiveness of FOLFOX with Sorafenib as a first-line treatment for aHCC in real-life practice. METHODS A retrospective aHCC cohort from four Thai hospitals was investigated for patients who received FOLFOX or Sorafenib between 2013-2019. Multiple imputation by chained equations addressed missing covariate data in a treatment effect model using Weight-adjusted-censoring inverse-probability-weighted regression adjustment; overall survival (OS) and progression-free survival (PFS) were estimated. RESULTS A total of 504 patients were included, (Sorafenib [n = 382] and FOLFOX [n = 122]). The treatment effect model estimated a median OS for Sorafenib and FOLFOX of 11.38 and 8.22 months, representing a significantly shorter OS (95% confidence interval) of -3.16 (-6.21, -0.11) months for FOLFOX, p = 0.042. A significant shorter median PFS of FOLFOX to Sorafenib of -2.13 (-3.03, -1.24) months, p < 0.001, was reported. CONCLUSION Despite significantly shorter median OS and PFS than Sorafenib, FOLFOX still extended OS by 8.22 months. This evidence may offer clinical utility to physicians considering treatment options for aHCC in low resource settings.
Collapse
Affiliation(s)
- Songporn Oranratnachai
- Department of Clinical Epidemiology and Biostatistics, Faculty of Medicine Ramathibodi HospitalMahidol UniversityBangkokThailand,Oncology Clinic, Sriphat Medical Center, Faculty of MedicineChiang Mai UniversityChiang MaiThailand
| | - Sasivimol Rattanasiri
- Department of Clinical Epidemiology and Biostatistics, Faculty of Medicine Ramathibodi HospitalMahidol UniversityBangkokThailand
| | - Ekaphop Sirachainan
- Division of Medical Oncology, Department of Medicine, Faculty of Medicine Ramathibodi HospitalMahidol UniversityBangkokThailand
| | - Amarit Tansawet
- Department of Clinical Epidemiology and Biostatistics, Faculty of Medicine Ramathibodi HospitalMahidol UniversityBangkokThailand,Department of Surgery, Faculty of Medicine Vajira HospitalNavamindradhiraj UniversityBangkokThailand
| | | | - Gareth J. McKay
- Centre for Public Health, School of Medicine, Dentistry and Biomedical SciencesQueen's University BelfastBelfastUK
| | - John Attia
- Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, Hunter Medical Research InstituteUniversity of NewcastleNew LambtonNew South WalesAustralia
| | - Ammarin Thakkinstian
- Department of Clinical Epidemiology and Biostatistics, Faculty of Medicine Ramathibodi HospitalMahidol UniversityBangkokThailand
| |
Collapse
|
|
5
|
Fan Y, Xue H, Zheng H. Systemic Therapy for Hepatocellular Carcinoma: Current Updates and Outlook. J Hepatocell Carcinoma 2022; 9:233-263. [PMID: 35388357 PMCID: PMC8977221 DOI: 10.2147/jhc.s358082] [Citation(s) in RCA: 34] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Accepted: 03/15/2022] [Indexed: 01/27/2023] Open
Abstract
Hepatocellular carcinoma (HCC) has emerged the culprit of cancer-related mortality worldwide with its dismal prognosis climbing. In recent years, ground-breaking progress has been made in systemic therapy for HCC. Targeted therapy based on specific signaling molecules, including sorafenib, lenvatinib, regorafenib, cabozantinib, and ramucirumab, has been widely used for advanced HCC (aHCC). Immunotherapies such as pembrolizumab and nivolumab greatly improve the survival of aHCC patients. More recently, synergistic combination therapy has boosted first-line (atezolizumab in combination with bevacizumab) and second-line (ipilimumab in combination with nivolumab) therapeutic modalities for aHCC. This review aims to summarize recent updates of systemic therapy relying on the biological mechanisms of HCC, particularly highlighting the approved agents for aHCC. Adjuvant and neoadjuvant therapy, as well as a combination with locoregional therapies (LRTs), are also discussed. Additionally, we describe the promising effect of traditional Chinese medicine (TCM) as systemic therapy on HCC. In this setting, the challenges and future directions of systemic therapy for HCC are also explored.
Collapse
Affiliation(s)
- Yinjie Fan
- College of Integrated Chinese and Western Medicine, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, 110847, People’s Republic of China
- Department of Oncology and Experimental Center, the Affiliated Hospital of Chengde Medical University, Chengde, Hebei, 067000, People’s Republic of China
| | - Hang Xue
- Department of Oncology and Experimental Center, the Affiliated Hospital of Chengde Medical University, Chengde, Hebei, 067000, People’s Republic of China
| | - Huachuan Zheng
- Department of Oncology and Experimental Center, the Affiliated Hospital of Chengde Medical University, Chengde, Hebei, 067000, People’s Republic of China
- Correspondence: Huachuan Zheng, Department of Oncology and Experimental Center, the Affiliated Hospital of Chengde Medical University, Chengde, Hebei, 067000, People’s Republic of China, Tel +86-0314-2279458, Fax +86-0314-2279458, Email
| |
Collapse
|
|
6
|
Wu TC, Shen YC, Cheng AL. Evolution of systemic treatment for advanced hepatocellular carcinoma. Kaohsiung J Med Sci 2021; 37:643-653. [PMID: 34213069 DOI: 10.1002/kjm2.12401] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Revised: 05/09/2021] [Accepted: 05/11/2021] [Indexed: 12/30/2022] Open
Abstract
Advanced hepatocellular carcinoma (HCC) was considered an inherently refractory tumor in the chemotherapy era (1950-2000). However, systemic therapy has evolved to molecular targeted therapy and immunotherapy, and nine treatment regimens have been approved worldwide during the past 20 years. The approved regimens target tumor angiogenesis or tumor immunity, the two cancer hallmarks. Recently, the combination of atezolizumab (antiprogrammed cell death ligand 1) and bevacizumab (anti-vascular endothelial growth factor) has improved the efficacy of systemic therapy in treating advanced HCC without excessive toxicities or deterioration of quality of life. This review summarizes the major advances in systemic therapy and provides future perspectives on the next-generation systemic therapy for advanced HCC.
Collapse
Affiliation(s)
- Tsung-Che Wu
- Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan
| | - Ying-Chun Shen
- Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.,Department of Medical Oncology, National Taiwan University Cancer Center, Taipei, Taiwan.,Graduate Institute of Oncology, School of Medicine, National Taiwan University, Taipei, Taiwan
| | - Ann-Lii Cheng
- Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.,Department of Medical Oncology, National Taiwan University Cancer Center, Taipei, Taiwan.,Graduate Institute of Oncology, School of Medicine, National Taiwan University, Taipei, Taiwan
| |
Collapse
|
|
7
|
Piñero F, Silva M, Iavarone M. Sequencing of systemic treatment for hepatocellular carcinoma: Second line competitors. World J Gastroenterol 2020; 26:1888-1900. [PMID: 32390700 PMCID: PMC7201145 DOI: 10.3748/wjg.v26.i16.1888] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2019] [Revised: 03/27/2020] [Accepted: 04/04/2020] [Indexed: 02/06/2023] Open
Abstract
During the last decades, further knowledge of hepatocellular carcinoma (HCC) molecular mechanisms has led to development of effective systemic treatments including tyrosine kinase inhibitors (TKIs) and immunotherapy. In this review, we describe first and second line systemic treatment options for advanced HCC. Several trials have evaluated new drugs for the treatment of HCC patients: In first line, lenvatinib resulted non-inferior to sorafenib and it can be used as alternative, even in the lack of evidence for sequential treatment options in second line after lenvatinib. Recently, atezolizumab plus bevacizumab have shown superiority over sorafenib in first-line. Sorafenib-regorafenib sequential administration in selected patients has opened a new paradigm of treatment in advanced HCC with a life expectancy exceeding two years. Other TKIs for second line treatment include cabozantinib and ramucirumab (specifically for patients with Alpha-fetoprotein values ≥ 400 ng/mL). The combination of TKIs with immunotherapy may represent a big step forward for these patients in the near future.
Collapse
Affiliation(s)
- Federico Piñero
- Hospital Universitario Austral, Facultad de Ciencias Biomédicas, Universidad Austral, Buenos Aires B1629HJ, Argentina
- Latin American Liver Research Educational and Awareness Network, Buenos Aires B1629HJ, Argentina
| | - Marcelo Silva
- Hospital Universitario Austral, Facultad de Ciencias Biomédicas, Universidad Austral, Buenos Aires B1629HJ, Argentina
- Latin American Liver Research Educational and Awareness Network, Buenos Aires B1629HJ, Argentina
| | - Massimo Iavarone
- Division of Gastroenterology and Hepatology, CRC “A.M. e A. Migliavacca” Center for the Study of Liver Disease, University of Milan, Fondazione IRCCS Ca’ Granda Maggiore Hospital, Milan 20121, Italy
| |
Collapse
|
|
8
|
Chagas AL, Mattos AAD, Carrilho FJ, Bittencourt PL, Vezozzo DCP, Horvat N, Rocha MDS, Alves VAF, Coral GP, Alvares-DA-Silva MR, Barros FMDR, Menezes MR, Monsignore LM, Coelho FF, Silva RFD, Silva RDCMA, Boin IDFSF, D Albuquerque LAC, Garcia JHP, Felga GEG, Moreira AM, Braghiroli MIFM, Hoff PMG, Mello VBD, Dottori MF, Branco TP, Schiavon LDL, Costa TDFA. BRAZILIAN SOCIETY OF HEPATOLOGY UPDATED RECOMMENDATIONS FOR DIAGNOSIS AND TREATMENT OF HEPATOCELLULAR CARCINOMA. ARQUIVOS DE GASTROENTEROLOGIA 2020; 57:1-20. [PMID: 32294682 DOI: 10.1590/s0004-2803.202000000-20] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/13/2019] [Accepted: 12/19/2019] [Indexed: 02/06/2023]
Abstract
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. The Brazilian Society of Hepatology (SBH) published in 2015 its first recommendations about the management of HCC. Since then, new data have emerged in the literature, prompting the governing board of SBH to sponsor a single-topic meeting in August 2018 in São Paulo. All the invited experts were asked to make a systematic review of the literature reviewing the management of HCC in subjects with cirrhosis. After the meeting, all panelists gathered together for the discussion of the topics and the elaboration of updated recommendations. The text was subsequently submitted for suggestions and approval of all members of the Brazilian Society of Hepatology through its homepage. The present manuscript is the final version of the reviewed manuscript containing the recommendations of SBH.
Collapse
Affiliation(s)
- Aline Lopes Chagas
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo, SP, Brasil
- Universidade de São Paulo, Instituto do Câncer do Estado de São Paulo, São Paulo, SP, Brasil
| | - Angelo Alves de Mattos
- Universidade Federal de Ciências da Saúde de Porto Alegre e Irmandade da Santa Casa de Misericórdia de Porto Alegre, Porto Alegre, RS, Brasil
| | - Flair José Carrilho
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo, SP, Brasil
- Universidade de São Paulo, Instituto do Câncer do Estado de São Paulo, São Paulo, SP, Brasil
| | | | | | - Natally Horvat
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo, SP, Brasil
- Hospital Sírio-Libanês, São Paulo, SP, Brasil
| | - Manoel de Souza Rocha
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo, SP, Brasil
| | - Venâncio Avancini Ferreira Alves
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo, SP, Brasil
- Universidade de São Paulo, Instituto do Câncer do Estado de São Paulo, São Paulo, SP, Brasil
| | - Gabriela Perdomo Coral
- Universidade Federal de Ciências da Saúde de Porto Alegre e Irmandade da Santa Casa de Misericórdia de Porto Alegre, Porto Alegre, RS, Brasil
| | | | | | - Marcos Roberto Menezes
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo, SP, Brasil
- Universidade de São Paulo, Instituto do Câncer do Estado de São Paulo, São Paulo, SP, Brasil
- Hospital Sírio-Libanês, São Paulo, SP, Brasil
| | - Lucas Moretti Monsignore
- Universidade de São Paulo, Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto, São Paulo, SP, Brasil
| | | | - Renato Ferreira da Silva
- Faculdade de Medicina de São José do Rio Preto (FAMERP) e Hospital de Base de São José do Rio Preto (FUNFARME), São José do Rio Preto, SP, Brasil
| | - Rita de Cássia Martins Alves Silva
- Faculdade de Medicina de São José do Rio Preto (FAMERP) e Hospital de Base de São José do Rio Preto (FUNFARME), São José do Rio Preto, SP, Brasil
| | | | | | | | | | - Airton Mota Moreira
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo, SP, Brasil
- Universidade de São Paulo, Instituto do Câncer do Estado de São Paulo, São Paulo, SP, Brasil
| | | | - Paulo Marcelo Gehm Hoff
- Universidade de São Paulo, Instituto do Câncer do Estado de São Paulo, São Paulo, SP, Brasil
| | | | | | - Tiago Pugliese Branco
- Universidade de São Paulo, Instituto do Câncer do Estado de São Paulo, São Paulo, SP, Brasil
| | | | | |
Collapse
|
|
9
|
Abou-Alfa GK, Jarnagin W, El Dika I, D'Angelica M, Lowery M, Brown K, Ludwig E, Kemeny N, Covey A, Crane CH, Harding J, Shia J, O'Reilly EM. Liver and Bile Duct Cancer. ABELOFF'S CLINICAL ONCOLOGY 2020:1314-1341.e11. [DOI: 10.1016/b978-0-323-47674-4.00077-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
|
|
10
|
Gans JH, Lipman J, Golowa Y, Kinkhabwala M, Kaubisch A. Hepatic Cancers Overview: Surgical and Chemotherapeutic Options, How Do Y-90 Microspheres Fit in? Semin Nucl Med 2019; 49:170-181. [DOI: 10.1053/j.semnuclmed.2019.01.001] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
|
|
11
|
Sorafenib alone vs. sorafenib plus GEMOX as 1 st-line treatment for advanced HCC: the phase II randomised PRODIGE 10 trial. Br J Cancer 2019; 120:896-902. [PMID: 30944458 PMCID: PMC6734663 DOI: 10.1038/s41416-019-0443-4] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2018] [Revised: 03/08/2019] [Accepted: 03/14/2019] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Sorafenib remains one major first-line therapeutic options for advanced hepatocellular carcinoma (aHCC), with modest efficacy. We investigated the addition of gemcitabine and oxaliplatin (GEMOX) to sorafenib in aHCC patients. METHODS Our multicentre phase II trial randomised aHCC first-line patients to sorafenib (400 mg BID) or sorafenib-GEMOX every 2 weeks (1000 mg/m2 gemcitabine; 100 mg/m2 oxaliplatin). Primary endpoint was the 4-month progression-free survival (PFS) rate. RESULTS Ninety-four patients were randomised (sorafenib-GEMOX: n = 48; sorafenib: n = 46). Median age was 64 years, PS 0 (69%) or 1 (31%), 63% patients had cirrhosis, 29% portal vein thrombosis and 70% extra-hepatic disease. Median duration of sorafenib treatment was 4 months (1-51); median number of GEMOX cycles was 7 (1-16). The 4-month PFS rates were 64% and 61% in the sorafenib-GEMOX and sorafenib arms, respectively; median PFS and OS were 6.2 (95% CI: 3.8-6.8) and 13.5 (7.5-16.2) months, and 4.6 (3.9-6.2) months and 14.8 (12.2-22.2), respectively. The ORR/DCR were 9%/70% and 15%/77% in the sorafenib-GEMOX and sorafenib alone arms, respectively. Main toxicities were (sorafenib-GEMOX/sorafenib) neutropenia (23%/0), thrombocytopenia (33%/0), diarrhoea (18%/9), peripheral neuropathy (5%/0) and hand-foot syndrome (5%/18). CONCLUSIONS Addition of GEMOX had an inpact on ORR and was well-tolerated as frontline systemic therapy. The benefit on PFS seems moderate; no subsequent study was planned.
Collapse
|
|
12
|
Wei Y, Dai F, Zhao T, Tao C, Wang L, Ye W, Zhao W. Transcatheter arterial chemoembolization monotherapy vs combined transcatheter arterial chemoembolization-percutaneous microwave coagulation therapy for massive hepatocellular carcinoma (≥10 cm). Cancer Manag Res 2018; 10:5273-5282. [PMID: 30464624 PMCID: PMC6219403 DOI: 10.2147/cmar.s172395] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Background The prognosis of massive hepatocellular carcinomas (MHCCs; ≥10 cm) remains worse. Purpose The aim of this study was to evaluate the clinical benefits of transcatheter arterial chemoembolization (TACE) or TACE combined with percutaneous microwave coagulation therapy (PMCT) and the long-term survival rate of MHCC patients treated with these techniques. Patients and methods A retrospective study was performed using data involving 102 MHCC patients admitted to the Second Hospital of Nanjing from September 2010 to August 2015. The median interval between treatments and overall survival (OS) was hierarchically analyzed using log-rank tests. Multivariate analysis was done using Cox regression model analysis. Results The median survival time of MHCC patients was 3 months (range, 1–10 months) in the palliative group, 3 months (range, 1–39 months) in the TACE group, and 7.5 months (range, 3–30 months) in the TACE–PMCT group (P=0.038). The 6-, 12-, and 18-month OS rates for MHCC patients were 15%, 0%, and 0% in the palliative group, 30%, 25.63%, and 17.97% in the TACE group, and 50%, 41.67%, and 16.67% in the TACE–PMCT group, respectively (P=0.0467). In addition, TACE sessions had positive correlation with the survival time of MHCC patients (rho = 0.462, P<0.001). TACE treatment more than three times (HR =0.145, P<0.001) was an independent predictor of the survival of MHCC patients, which was identified by the Cox regression model analysis. Conclusions These results indicated that TACE–PMCT treatment in MHCC patients had advantages in prolonging OS and improving liver function. Multiple TACE treatments might be a suitable treatment for the MHCC patients.
Collapse
Affiliation(s)
- Yanyan Wei
- Liver Disease Department, The Second Hospital of Nanjing, Medical School of Southeast University, Nanjing, China, ;
| | - Feng Dai
- Liver Disease Department, The Second Hospital of Nanjing, Medical School of Southeast University, Nanjing, China, ;
| | - Tianhui Zhao
- Liver Disease Department, The Second Hospital of Nanjing, Medical School of Southeast University, Nanjing, China, ;
| | - Chen Tao
- Liver Disease Department, The Second Hospital of Nanjing, Medical School of Southeast University, Nanjing, China, ;
| | - Lili Wang
- Liver Disease Department, The Second Hospital of Nanjing, Medical School of Southeast University, Nanjing, China, ;
| | - Wei Ye
- Liver Disease Department, The Second Hospital of Nanjing, Medical School of Southeast University, Nanjing, China, ;
| | - Wei Zhao
- Liver Disease Department, The Second Hospital of Nanjing, Medical School of Southeast University, Nanjing, China, ;
| |
Collapse
|
|
13
|
Eatrides J, Wang E, Kothari N, Kim R. Role of Systemic Therapy and Future Directions for Hepatocellular Carcinoma. Cancer Control 2018; 24:1073274817729243. [PMID: 28975834 PMCID: PMC5937243 DOI: 10.1177/1073274817729243] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is an aggressive tumor that often arises in the setting of liver cirrhosis. Although early-stage disease is often amenable for surgical resection, transplant, or locoregional therapies, many patients are diagnosed at an advanced stage or have poor liver reserve. Systemic therapy is the mainstay of treatment for these patients. At present, the only approved therapy for the treatment of advanced disease is the tyrosine multikinase inhibitor sorafenib. Candidacy for treatment is based on liver reserve. Novel agents for the treatment of this disease are urgently needed. In this article, we review systemic therapy trials and upcoming data for the treatment of HCC.
Collapse
Affiliation(s)
- Jennifer Eatrides
- 1 Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA
| | - Emilie Wang
- 1 Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA
| | - Nishi Kothari
- 1 Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA
| | - Richard Kim
- 1 Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA
| |
Collapse
|
|
14
|
Brandi G, De Rosa F, Bolondi L, Agostini V, Di Girolamo S, Nobili E, Biasco G. Durable Complete Response of Hepatocellular Carcinoma after Metronomic Capecitabine. TUMORI JOURNAL 2018. [DOI: 10.1177/548.6527] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Background Hepatocellular carcinoma (HCC) is a highly vascular tumor which is poorly responsive to standard systemic chemotherapy. Recently, various antiangiogenic targeted agents have shown promising activity at different levels of evidence in patients with advanced HCC, suggesting that such treatments might be effective. Case report Since chemotherapy administered with metronomic schedules inhibits angiogenesis, we treated a 64-year-old man with advanced HCC with metronomic capecitabine. After only two months of treatment the HCC nodules disappeared on ultrasonography. This finding was confirmed by a computed tomography scan. After more than three years the patient is still in treatment with minimal toxicity and maintains a complete remission. Conclusions Our case report suggests that metronomic capecitabine may be effective in advanced HCC patients while being also well tolerated. This is important, given the frequent comorbidities of HCC patients. Free full text available at www.tumorionline.it
Collapse
Affiliation(s)
- Giovanni Brandi
- Department of Hematology and Oncological Sciences “L. e A. Seràgnoli”, University of Bologna, Bologna, Italy
| | - Francesco De Rosa
- Department of Hematology and Oncological Sciences “L. e A. Seràgnoli”, University of Bologna, Bologna, Italy
| | - Luigi Bolondi
- Department of Internal Medicine, Policlinico Sant'Orsola Malpighi, University of Bologna, Bologna, Italy
| | - Valentina Agostini
- Department of Hematology and Oncological Sciences “L. e A. Seràgnoli”, University of Bologna, Bologna, Italy
| | - Stefania Di Girolamo
- Department of Hematology and Oncological Sciences “L. e A. Seràgnoli”, University of Bologna, Bologna, Italy
| | - Elisabetta Nobili
- Department of Hematology and Oncological Sciences “L. e A. Seràgnoli”, University of Bologna, Bologna, Italy
| | - Guido Biasco
- Department of Hematology and Oncological Sciences “L. e A. Seràgnoli”, University of Bologna, Bologna, Italy
| |
Collapse
|
|
15
|
Posadas K, Ankola A, Yang Z, Yee NS. Tumor Molecular Profiling for an Individualized Approach to the Treatment of Hepatocellular Carcinoma: A Patient Case Study. Biomedicines 2018; 6:46. [PMID: 29673151 PMCID: PMC6027424 DOI: 10.3390/biomedicines6020046] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2018] [Revised: 04/07/2018] [Accepted: 04/09/2018] [Indexed: 12/29/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is increasing in incidence, and the associated mortality rate remains among the highest. For advanced HCC, sorafenib has been shown to slightly prolong survival, and regorafenib and nivolumab, both recently approved by the United States Food and Drug Administration (FDA), may produce clinical benefits to a limited extent. Systemic chemotherapy has been shown to produce a modest response, but there is no clinically valid biomarker that can be used to predict which patients may benefit. In this case study, we present two patients with metastatic HCC, they received systemic treatment using capecitabine, oxaliplatin, and either bevacizumab or sorafenib. The tumor response to treatment was determined by the progression-free survival (PFS). Molecular profiling of the tumors showed differential expression of biochemical markers and different mutational status of the TP53 and β-catenin (CTNNB1) genes. We hypothesize that the PFS correlates with the tumor molecular profiles, which may be predictive of the therapeutic response to systemic chemotherapy. Further investigation is indicated to correlate tumor biomarkers and treatment responses, with the objective of personalizing the therapies for patients with advanced HCC.
Collapse
Affiliation(s)
- Kristine Posadas
- Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
| | - Anita Ankola
- Department of Radiology, Penn State Health Milton S. Hershey Medical Center, Hershey, PA 17033, USA.
| | - Zhaohai Yang
- Department of Pathology, Penn State Health Milton S. Hershey Medical Center, Hershey, PA 17033, USA.
| | - Nelson S Yee
- Division of Hematology-Oncology, Department of Medicine, Penn State Health Milton S. Hershey Medical Center; Experimental Therapeutics Program, Penn State Cancer Institute, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
| |
Collapse
|
|
16
|
Le Grazie M, Biagini MR, Tarocchi M, Polvani S, Galli A. Chemotherapy for hepatocellular carcinoma: The present and the future. World J Hepatol 2017; 9:907-920. [PMID: 28824742 PMCID: PMC5545136 DOI: 10.4254/wjh.v9.i21.907] [Citation(s) in RCA: 144] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2017] [Revised: 06/20/2017] [Accepted: 07/03/2017] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver. Its relationship to chronic liver diseases, in particular cirrhosis, develops on a background of viral hepatitis, excessive alcohol intake or metabolic steatohepatitis, leads to a high incidence and prevalence of this neoplasia worldwide. Despite the spread of HCC, its treatment it’s still a hard challenge, due to high rate of late diagnosis and to lack of therapeutic options for advanced disease. In fact radical surgery and liver transplantation, the most radical therapeutic approaches, are indicated only in case of early diagnosis. Even local therapies, such as transarterial chemoembolization, find limited indications, leading to an important problem regarding treatment of advanced disease. In this situation, until terminal HCC occurs, systemic therapy is the only possible approach, with sorafenib as the only standard treatment available. Anyway, the efficacy of this drug is limited and many efforts are necessary to understand who could benefit more with this treatment. Therefore, other molecules for a targeted therapy were evaluated, but only regorafenib showed promising results. Beside molecular target therapy, also cytotoxic drugs, in particular oxaliplatin- and gemcitabine-based regimens, and immune-checkpoint inhibitors were tested with interesting results. The future of the treatment of this neoplasia is linked to our ability to understand its mechanisms of resistance and to find novel therapeutic targets, with the objective to purpose individualized approaches to patients affected by advanced HCC.
Collapse
|
|
17
|
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver cancer with poor prognosis. The incidence of HCC and HCC-related deaths have increased over the last several decades. However, the treatment options for advanced HCC are very limited. Sorafenib remains the only drug approved for systemic treatment for advanced HCC. However, prior to sorafenib era conventional cytotoxic chemotherapies have been studied in advanced HCC. In this review, clinical studies of systemic chemotherapy for advanced HCC will be summarized and discussed.
Collapse
Affiliation(s)
- Dae Won Kim
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center, Tampa, FL 33612, USA
| | - Chetasi Talati
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center, Tampa, FL 33612, USA
| | - Richard Kim
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center, Tampa, FL 33612, USA
| |
Collapse
|
|
18
|
Liu L, Zheng YH, Han L, Qin SK. Efficacy and safety of the oxaliplatin-based chemotherapy in the treatment of advanced primary hepatocellular carcinoma: A meta-analysis of prospective studies. Medicine (Baltimore) 2016; 95:e4993. [PMID: 27749557 PMCID: PMC5059059 DOI: 10.1097/md.0000000000004993] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND Many clinical studies have demonstrated the survival benefits of oxaliplatin-based chemotherapy for advanced hepatocellular carcinoma patients. Therefore, we aim to evaluate the efficacy and safety of oxaliplatin-based chemotherapy in patients with advanced hepatocellular carcinoma by conducting a meta-analysis of prospective studies. METHODS A comprehensive literature search was performed using the PubMed, Cochrane Library, EMBASE, and Web of Science databases from their inception to June 2016. Only prospective studies evaluating oxaliplatin-based chemotherapy in patients with advanced hepatocellular carcinoma were selected. The main outcomes included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and main adverse events. RESULTS Ten prospective studies involving 525 patients were included. The pooled ORR, 1-year PFS, and OS were 14.4% (95% confidence interval [CI] 9.2-19.6%), 9.3% (95%CI 10-28%), and 35.7% (95%CI 27-44%), respectively, for oxaliplatin-based chemotherapy. The median PFS and OS were 4.7 and 9.4 months, respectively. The incidences of grade 3/4 toxicities of neutropenia, thrombopenia, anemia, neurotoxicity, diarrhea, and nausea/vomiting were 17.2%, 9.2%, 6.0%, 4.8%, 3.1%, and 1.8%, respectively. Subgroup analysis revealed that the pooled ORR was 13.9% (95%CI 6.8-21%) in Asian patients and 12.8% (95%CI 6.8-18.7%) in Western patients. For Asian patients, the median PFS and OS were 4.2 and 9.2 months, and the 1-year PFS and OS were 12.5% and 30.5%, respectively. For Western patients, the median PFS and OS were 4.7 and 9.5 months, and the 1-year PFS and OS were 19.6% and 42.4%, respectively. There were no significant differences in the ORR, 1-year PFS, and OS (P > 0.05) between Asian and Western patients. CONCLUSIONS Oxaliplatin-based chemotherapy appears to be effective and safe for the treatment of advanced hepatocellular carcinoma.
Collapse
Affiliation(s)
- Lin Liu
- Department of Oncology, Zhong-Da Hospital, School of Medicine, Southeast University
- Department of Oncology, 81st Hospital of the Chinese People's Liberation Army, Nanjing, Jiangsu, China
- Correspondence: Lin Liu, Department of Oncology, Zhong-Da Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, China (e-mail: ); Shu-Kui Qin, Department of Oncology, the 81 Hospital of the Chinese People's Liberation Army, Nanjing, Jiangsu, China (e-mail: )
| | - Ying-hui Zheng
- Department of Oncology, Zhong-Da Hospital, School of Medicine, Southeast University
| | - Li Han
- Department of Oncology, Zhong-Da Hospital, School of Medicine, Southeast University
| | - Shu-Kui Qin
- Department of Oncology, 81st Hospital of the Chinese People's Liberation Army, Nanjing, Jiangsu, China
- Correspondence: Lin Liu, Department of Oncology, Zhong-Da Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, China (e-mail: ); Shu-Kui Qin, Department of Oncology, the 81 Hospital of the Chinese People's Liberation Army, Nanjing, Jiangsu, China (e-mail: )
| |
Collapse
|
|
19
|
Shrum B, Costello P, McDonald W, Howlett C, Donnelly M, McAlister VC. In vitro three dimensional culture of hepatocellular carcinoma to measure prognosis and responsiveness to chemotherapeutic agents. Hepatobiliary Surg Nutr 2016; 5:204-8. [PMID: 27275461 DOI: 10.21037/hbsn.2016.01.01] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
BACKGROUND Understanding the prognosis of hepatocellular carcinoma (HCC) informs plans for care. Tumor morphology and molecular markers have been correlated with outcomes. Three-dimensional tissue culture (3DTC) allows for direct in vitro measurement of a tumor's ability to grow and metastasize. The impact of chemotherapeutic agents, alone or in combinations, may also be measured. METHODS All patients with a presumed diagnosis of HCC were eligible for this study including those undergoing resection, chemoembolization and transplantation. Concomitant diseases and outcomes were recorded. One mm(3) HCC specimens were grown in multiwell plates containing gel media, without and with chemotherapeutic agents. RESULTS Tumors were sampled from 17 patients. Only 13 had HCC, all of whom had liver transplantation. Of the confirmed HCC patients, 6 (46%) are alive and disease free 82 months following transplantation, 1 (7%) is alive with recurrence of disease and 6 (46%) died, with a mean survival of 12 months post liver transplant. Ten of thirteen 3DTC samples grew, having an average migration distance of 108.3µm in the first 24 hours. Two of three patients who had prior chemoembolization had successful 3DTC. Migration distances (µm) were 188.8±104.3, 104.5±111.7 and 39.6±32.4 for tumors categorized as high, intermediate and low grade, respectively. Tumor migration was inhibited by irinotecan, paclitaxel and docetaxel (-68%±7%, -61%±19% and -60%±21%, respectively) whereas the effect was variable with 5 fluorouracil (5FU) and doxorubicin (-12%±51% and 9%±76%, respectively). CONCLUSIONS It is feasible to grow tissue from HCC in 3DTC to study the tumor's capacity to grow and migrate and its responsiveness to commonly used chemotherapeutic protocols.
Collapse
Affiliation(s)
- Brad Shrum
- 1 General Surgery Experimental Laboratory, University Hospital, London, ON, Canada ; 2 Department of Pathology, London Health Sciences Centre, London, ON, Canada
| | - Penny Costello
- 1 General Surgery Experimental Laboratory, University Hospital, London, ON, Canada ; 2 Department of Pathology, London Health Sciences Centre, London, ON, Canada
| | - Warren McDonald
- 1 General Surgery Experimental Laboratory, University Hospital, London, ON, Canada ; 2 Department of Pathology, London Health Sciences Centre, London, ON, Canada
| | - Christopher Howlett
- 1 General Surgery Experimental Laboratory, University Hospital, London, ON, Canada ; 2 Department of Pathology, London Health Sciences Centre, London, ON, Canada
| | - Marisa Donnelly
- 1 General Surgery Experimental Laboratory, University Hospital, London, ON, Canada ; 2 Department of Pathology, London Health Sciences Centre, London, ON, Canada
| | - Vivian C McAlister
- 1 General Surgery Experimental Laboratory, University Hospital, London, ON, Canada ; 2 Department of Pathology, London Health Sciences Centre, London, ON, Canada
| |
Collapse
|
|
20
|
Gao L, Wang XD, Niu YY, Duan DD, Yang X, Hao J, Zhu CH, Chen D, Wang KX, Qin XM, Wu XZ. Molecular targets of Chinese herbs: a clinical study of hepatoma based on network pharmacology. Sci Rep 2016; 6:24944. [PMID: 27143508 PMCID: PMC4855233 DOI: 10.1038/srep24944] [Citation(s) in RCA: 68] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2016] [Accepted: 04/07/2016] [Indexed: 12/15/2022] Open
Abstract
Traditional Chinese medicine (TCM) has been used to treat tumors for years and has been demonstrated to be effective. However, the underlying molecular mechanisms of herbs remain unclear. This study aims to ascertain molecular targets of herbs prolonging survival time of patients with advanced hepatocellular carcinoma (HCC) based on network pharmacology, and to establish a research method for accurate treatment of TCM. The survival benefit of TCM treatment with Chinese herbal medicine (CHM) was proved by Kaplan-Meier method and Cox regression analysis among 288 patients. The correlation between herbs and survival time was performed by bivariate correlation analysis. Network pharmacology method was utilized to construct the active ingredient-target networks of herbs that were responsible for the beneficial effects against HCC. Cox regression analysis showed CHM was an independent favorable prognostic factor. The median survival time was 13 months and the 5-year overall survival rates were 2.61% in the TCM group, while there were 6 months, 0 in the non-TCM group. Correlation analysis demonstrated that 8 herbs closely associated with prognosis. Network pharmacology analysis revealed that the 8 herbs regulated multiple HCC relative genes, among which the genes affected proliferation (KRAS, AKT2, MAPK), metastasis (SRC, MMP), angiogenesis (PTGS2) and apoptosis (CASP3) etc.
Collapse
Affiliation(s)
- Li Gao
- Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan 030006, PR China
| | - Xiao-dong Wang
- Tianjin Medical University, Tianjin, 300070, China
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China
| | - Yang-yang Niu
- Tianjin Medical University, Tianjin, 300070, China
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China
| | - Dan-dan Duan
- Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan 030006, PR China
- College of Chemistry and Chemical Engineering, Shanxi University, Taiyuan 030006, PR China
| | - Xue Yang
- Tianjin Medical University, Tianjin, 300070, China
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China
| | - Jian Hao
- Tianjin Medical University, Tianjin, 300070, China
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China
| | - Cui-hong Zhu
- Tianjin Medical University, Tianjin, 300070, China
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China
| | - Dan Chen
- Department of Pharmacology, Basic Medical College, Tianjin Medical University, Tianjin, 300070, China
| | - Ke-xin Wang
- Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan 030006, PR China
- College of Chemistry and Chemical Engineering, Shanxi University, Taiyuan 030006, PR China
| | - Xue-mei Qin
- Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan 030006, PR China
| | - Xiong-zhi Wu
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China
- Tianjin People’s Hospital, NO.190 Jieyuan Road, Hongqiao, District, 300000, China
| |
Collapse
|
|
21
|
Nguyen K, Jack K, Sun W. Hepatocellular Carcinoma: Past and Future of Molecular Target Therapy. Diseases 2015; 4:E1. [PMID: 28933381 PMCID: PMC5456309 DOI: 10.3390/diseases4010001] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2015] [Revised: 12/03/2015] [Accepted: 12/16/2015] [Indexed: 12/17/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most common causes of cancer related mortality worldwide. The incidence of HCC has been increasing annually. Viral infection, alcohol usage, and other causes of cirrhosis have been identified as major risk factors for HCC development. The underlying pathogenesis has not been as well defined. There have been multiple hypotheses to the specific mechanisms of hepatocarcinogenesis and they share the common theme of chronic inflammation, increase oxidative stress, and genomic alteration. Therapeutic options of HCC have been primarily local and/or regional including transplantation, resection, and radial frequency ablation, chemoembolization or radio-embolization. For unresectable or metastatic disease, the options are limited. Conventional chemotherapeutic options have been noted to have limited benefit. Sorafenib has been the one and only systemic therapy which has demonstrated modest overall survival benefit. This has led to more extensive research with focus on targeted therapy. Numerous pre-clinical and early phase clinical studies have been noted but failed to show efficacy in later phase clinical trials. In an effort to identify new potential therapeutic options, new understanding of underlying pathways to hepatocarcinogenesis should be one of the main focuses. This leads to development of more molecularly targeted agents to specific pathways, and immunotherapy. This article provides a review of major studies of molecular targeted agents which attempts to target these specific pathways in HCC.
Collapse
Affiliation(s)
- Khanh Nguyen
- University of Pittsburgh Medical Center, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, 5150 Center Ave. 5th floor, Pittsburgh, PA 15232, USA.
| | - Kerri Jack
- University of Pittsburgh Medical Center, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, 5150 Center Ave. 5th floor, Pittsburgh, PA 15232, USA.
| | - Weijing Sun
- University of Pittsburgh Medical Center, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, 5150 Center Ave. 5th floor, Pittsburgh, PA 15232, USA.
| |
Collapse
|
|
22
|
Qin S, Gong X. Progression of systemic chemotherapy with oxaliplatin-containing regimens for advanced hepatocellular carcinoma in China. Hepat Oncol 2015; 3:71-81. [PMID: 30191027 DOI: 10.2217/hep.15.42] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2015] [Accepted: 07/29/2015] [Indexed: 12/29/2022] Open
Abstract
Hepatocellular carcinoma (HCC) characterized by insidious onset is a highly invasive malignance and has a rapid progress. The majority of patients, especially in Asian countries, present with locally advanced or distant metastatic disease at diagnosis and are not eligible for local treatment. Before the publication of the EACH study results showing the survival benefits of the FOLFOX 4 regimen in Chinese patients with advanced HCC, no chemotherapeutical drug or regimen was considered as systemic chemotherapy standard for this group of patients due to the lack of evidence-based recommendations. Oxaliplatin-containing regimens have shown clinical activity against advanced HCC with an acceptable safety profile. The aim of this article is to present a review of the scientific evidence mainly originating from China that supports the recommendation of oxaliplatin-based regimens for the treatment of Chinese patients with advanced HCC.
Collapse
Affiliation(s)
- Shukui Qin
- Chinese People's Liberation Army Cancer Center, Bayi Hospital, Nanjing, 210002, China
| | - Xinlei Gong
- Chinese People's Liberation Army Cancer Center, Bayi Hospital, Nanjing, 210002, China
| |
Collapse
|
|
23
|
2014 KLCSG-NCC Korea Practice Guideline for the Management of Hepatocellular Carcinoma. Gut Liver 2015; 9:267-317. [PMID: 25918260 PMCID: PMC4413964 DOI: 10.5009/gnl14460] [Citation(s) in RCA: 101] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2014] [Accepted: 03/09/2015] [Indexed: 12/23/2022] Open
Abstract
The guideline for the management of hepatocellular carcinoma (HCC) was first developed in 2003 and revised in 2009 by the Korean Liver Cancer Study Group and the National Cancer Center, Korea. Since then, many studies on HCC have been carried out in Korea and other countries. In particular, a substantial body of knowledge has been accumulated on diagnosis, staging, and treatment specific to Asian characteristics, especially Koreans, prompting the proposal of new strategies. Accordingly, the new guideline presented herein was developed on the basis of recent evidence and expert opinions. The primary targets of this guideline are patients with suspicious or newly diagnosed HCC. This guideline provides recommendations for the initial treatment of patients with newly diagnosed HCC.
Collapse
|
|
24
|
2014 Korean Liver Cancer Study Group-National Cancer Center Korea practice guideline for the management of hepatocellular carcinoma. Korean J Radiol 2015; 16:465-522. [PMID: 25995680 PMCID: PMC4435981 DOI: 10.3348/kjr.2015.16.3.465] [Citation(s) in RCA: 143] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2015] [Accepted: 04/02/2015] [Indexed: 02/07/2023] Open
Abstract
The guideline for the management of hepatocellular carcinoma (HCC) was first developed in 2003 and revised in 2009 by the Korean Liver Cancer Study Group and the National Cancer Center, Korea. Since then, many studies on HCC have been carried out in Korea and other countries. In particular, a substantial body of knowledge has been accumulated on diagnosis, staging, and treatment specific to Asian characteristics, especially Koreans, prompting the proposal of new strategies. Accordingly, the new guideline presented herein was developed on the basis of recent evidence and expert opinions. The primary targets of this guideline are patients with suspicious or newly diagnosed HCC. This guideline provides recommendations for the initial treatment of patients with newly diagnosed HCC.
Collapse
|
|
25
|
Chinese medicine herbal treatment based on syndrome differentiation improves the overall survival of patients with unresectable hepatocellular carcinoma. Chin J Integr Med 2014; 21:49-57. [PMID: 25533651 DOI: 10.1007/s11655-014-1767-9] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2013] [Indexed: 12/21/2022]
Abstract
OBJECTIVE To investigate the effects of Chinese medicine (CM) herbal treatment based on syndrome differentiation on patients with unresectable hepatocellular carcinoma (HCC). METHODS A total of 94 patients with unresectable HCC were reviewed between June 2008 and June 2011. Survival analysis was performed between patients who received CM with/without non-curative antitumor treatments of Western medicine (WM) (CM group, 30 cases) and patients who were not treated with CM but with non-curative antitumor treatments of WM or supportive treatment alone (non-CM group, 64 cases). Then, survival analysis was performed between patients treated with CM combined with non-curative antitumor treatments of WM (combination therapy group, 25 cases) and patients with non-curative antitumor treatments of WM alone (non-curative antitumor treatments group of WM, 52 cases). The survival analysis was performed by Kaplan-Meier method and prognostic factors for overall survival (OS) were assessed by the Cox proportional hazards regression model. RESULTS The median survival time (MST), 1- and 2-year survival rates of the CM group and the non-CM group were 36 months, 76.7%, 56.1% and 12 months, 48.4%, 26.6%, respectively. The Log-rank test revealed significant difference between the two groups in OS (P<0.01). Cox proportional multivariate analysis revealed that CM was an independent favorable prognostic factor for OS. The MST, 1- and 2-year survival rates of combination therapy group and non-curative antitumor treatments group of WM were 36 months, 76.0%, 55.5% and 13 months, 55.8%, 30.8%, respectively. There was significant difference in OS between the two groups (P=0.004). CONCLUSIONS CM herbs based on syndrome differentiation have positive effects on survival of patients with unresectable HCC. Furthermore, combination therapy of CM and WM are recommended in HCC treatment.
Collapse
|
|
26
|
Qin S, Cheng Y, Liang J, Shen L, Bai Y, Li J, Fan J, Liang L, Zhang Y, Wu G, Rau KM, Yang TS, Jian Z, Liang H, Sun Y. Efficacy and safety of the FOLFOX4 regimen versus doxorubicin in Chinese patients with advanced hepatocellular carcinoma: a subgroup analysis of the EACH study. Oncologist 2014; 19:1169-78. [PMID: 25223462 DOI: 10.1634/theoncologist.2014-0190] [Citation(s) in RCA: 67] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND The EACH study assessed the efficacy of oxaliplatin, 5-fluorouracil, and leucovorin (the FOLFOX4 regimen) compared with doxorubicin alone in terms of overall survival (OS), progression-free survival (PFS), and safety in patients with advanced hepatocellular carcinoma (HCC). We present the results of this study in Chinese patients. METHODS In a multicenter, open-label, randomized, phase III study (NCT00471965), 371 patients (279 patients from the People's Republic of China) were randomized 1:1 to receive either FOLFOX4 or doxorubicin until disease progression, intolerable toxicity, death, or surgical resection. RESULTS Baseline characteristics of the Chinese patients enrolled in the study were similar for the 2 treatment groups and in comparison with the whole EACH cohort. Median OS at the prespecified time point of treatment was 5.7 months with FOLFOX4 and 4.3 months with doxorubicin (hazard ratio [HR]: 0.74; 95% confidence interval [CI]: 0.55-0.98; p = .03). At the end of the follow-up period, median OS was 5.9 months with FOLFOX4 and 4.3 months with doxorubicin (HR: 0.75; 95% CI: 0.58-0.98; p = .03). Median PFS was 2.4 months and 1.7 months in the FOLFOX4 and doxorubicin groups, respectively (HR: 0.55; 95% CI: 0.45-0.78; p = .0002). The response rate (RR) and disease control rate (DCR) were significantly higher in the FOLFOX4 group than in the doxorubicin group (RR: 8.6% vs. 1.4%, p = .006; DCR: 47.1% vs. 26.6%, p = .0004). Hematological toxicity was more frequently reported in the FOLFOX4 group. CONCLUSION For Chinese HCC patients enrolled in the EACH study, FOLFOX4 significantly improved the RR and DCR and prolonged survival compared with doxorubicin. Systemic chemotherapy with oxaliplatin-based regimens may play an important role in the treatment of Chinese patients with advanced HCC.
Collapse
Affiliation(s)
- Shukui Qin
- People's Liberation Army Cancer Center, Bayi Hospital, Nanjing, People's Republic of China; Department of Medical Oncology, Jilin Province Cancer Hospital, Changchun, People's Republic of China; Department of Medical Oncology, The Affiliated Hospital of Medical College Qingdao University, Qingdao, People's Republic of China; Department of Gastrointestinal Medical Oncology, Peking University Cancer Hospital, Beijing, People's Republic of China; Department of Medical Oncology, Heilongjiang Province Cancer Hospital, Harbin, People's Republic of China; Medical Affairs, Sanofi China, Shanghai, People's Republic of China; Department of Hepatobiliary Surgery, Zhong Shan Hospital, Shanghai, People's Republic of China; Department of Hepatobiliary Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China; Department of Interventional Radiology, Sun Yat-sen University Cancer Hospital, Guangzhou, People's Republic of China; Department of Medical Oncology, Wuhan Union Hospital, Hubei, People's Republic of China; Department of Medical Oncology, Kaohsiung Chang-Gung Memorial Hospital, Kaohsiung, Taiwan, Republic of China; LinKou Medical Center, Chang-Gung Memorial Hospital, Taoyuan, Taiwan, Republic of China; Department of Hepatobiliary Surgery, Guangdong General Hospital, Guangzhou, People's Republic of China; Department of Medical Oncology, Southwest Hospital, Chongqing, People's Republic of China; Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing, People's Republic of China
| | - Ying Cheng
- People's Liberation Army Cancer Center, Bayi Hospital, Nanjing, People's Republic of China; Department of Medical Oncology, Jilin Province Cancer Hospital, Changchun, People's Republic of China; Department of Medical Oncology, The Affiliated Hospital of Medical College Qingdao University, Qingdao, People's Republic of China; Department of Gastrointestinal Medical Oncology, Peking University Cancer Hospital, Beijing, People's Republic of China; Department of Medical Oncology, Heilongjiang Province Cancer Hospital, Harbin, People's Republic of China; Medical Affairs, Sanofi China, Shanghai, People's Republic of China; Department of Hepatobiliary Surgery, Zhong Shan Hospital, Shanghai, People's Republic of China; Department of Hepatobiliary Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China; Department of Interventional Radiology, Sun Yat-sen University Cancer Hospital, Guangzhou, People's Republic of China; Department of Medical Oncology, Wuhan Union Hospital, Hubei, People's Republic of China; Department of Medical Oncology, Kaohsiung Chang-Gung Memorial Hospital, Kaohsiung, Taiwan, Republic of China; LinKou Medical Center, Chang-Gung Memorial Hospital, Taoyuan, Taiwan, Republic of China; Department of Hepatobiliary Surgery, Guangdong General Hospital, Guangzhou, People's Republic of China; Department of Medical Oncology, Southwest Hospital, Chongqing, People's Republic of China; Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing, People's Republic of China
| | - Jun Liang
- People's Liberation Army Cancer Center, Bayi Hospital, Nanjing, People's Republic of China; Department of Medical Oncology, Jilin Province Cancer Hospital, Changchun, People's Republic of China; Department of Medical Oncology, The Affiliated Hospital of Medical College Qingdao University, Qingdao, People's Republic of China; Department of Gastrointestinal Medical Oncology, Peking University Cancer Hospital, Beijing, People's Republic of China; Department of Medical Oncology, Heilongjiang Province Cancer Hospital, Harbin, People's Republic of China; Medical Affairs, Sanofi China, Shanghai, People's Republic of China; Department of Hepatobiliary Surgery, Zhong Shan Hospital, Shanghai, People's Republic of China; Department of Hepatobiliary Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China; Department of Interventional Radiology, Sun Yat-sen University Cancer Hospital, Guangzhou, People's Republic of China; Department of Medical Oncology, Wuhan Union Hospital, Hubei, People's Republic of China; Department of Medical Oncology, Kaohsiung Chang-Gung Memorial Hospital, Kaohsiung, Taiwan, Republic of China; LinKou Medical Center, Chang-Gung Memorial Hospital, Taoyuan, Taiwan, Republic of China; Department of Hepatobiliary Surgery, Guangdong General Hospital, Guangzhou, People's Republic of China; Department of Medical Oncology, Southwest Hospital, Chongqing, People's Republic of China; Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing, People's Republic of China
| | - Lin Shen
- People's Liberation Army Cancer Center, Bayi Hospital, Nanjing, People's Republic of China; Department of Medical Oncology, Jilin Province Cancer Hospital, Changchun, People's Republic of China; Department of Medical Oncology, The Affiliated Hospital of Medical College Qingdao University, Qingdao, People's Republic of China; Department of Gastrointestinal Medical Oncology, Peking University Cancer Hospital, Beijing, People's Republic of China; Department of Medical Oncology, Heilongjiang Province Cancer Hospital, Harbin, People's Republic of China; Medical Affairs, Sanofi China, Shanghai, People's Republic of China; Department of Hepatobiliary Surgery, Zhong Shan Hospital, Shanghai, People's Republic of China; Department of Hepatobiliary Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China; Department of Interventional Radiology, Sun Yat-sen University Cancer Hospital, Guangzhou, People's Republic of China; Department of Medical Oncology, Wuhan Union Hospital, Hubei, People's Republic of China; Department of Medical Oncology, Kaohsiung Chang-Gung Memorial Hospital, Kaohsiung, Taiwan, Republic of China; LinKou Medical Center, Chang-Gung Memorial Hospital, Taoyuan, Taiwan, Republic of China; Department of Hepatobiliary Surgery, Guangdong General Hospital, Guangzhou, People's Republic of China; Department of Medical Oncology, Southwest Hospital, Chongqing, People's Republic of China; Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing, People's Republic of China
| | - Yuxian Bai
- People's Liberation Army Cancer Center, Bayi Hospital, Nanjing, People's Republic of China; Department of Medical Oncology, Jilin Province Cancer Hospital, Changchun, People's Republic of China; Department of Medical Oncology, The Affiliated Hospital of Medical College Qingdao University, Qingdao, People's Republic of China; Department of Gastrointestinal Medical Oncology, Peking University Cancer Hospital, Beijing, People's Republic of China; Department of Medical Oncology, Heilongjiang Province Cancer Hospital, Harbin, People's Republic of China; Medical Affairs, Sanofi China, Shanghai, People's Republic of China; Department of Hepatobiliary Surgery, Zhong Shan Hospital, Shanghai, People's Republic of China; Department of Hepatobiliary Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China; Department of Interventional Radiology, Sun Yat-sen University Cancer Hospital, Guangzhou, People's Republic of China; Department of Medical Oncology, Wuhan Union Hospital, Hubei, People's Republic of China; Department of Medical Oncology, Kaohsiung Chang-Gung Memorial Hospital, Kaohsiung, Taiwan, Republic of China; LinKou Medical Center, Chang-Gung Memorial Hospital, Taoyuan, Taiwan, Republic of China; Department of Hepatobiliary Surgery, Guangdong General Hospital, Guangzhou, People's Republic of China; Department of Medical Oncology, Southwest Hospital, Chongqing, People's Republic of China; Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing, People's Republic of China
| | - Jianfeng Li
- People's Liberation Army Cancer Center, Bayi Hospital, Nanjing, People's Republic of China; Department of Medical Oncology, Jilin Province Cancer Hospital, Changchun, People's Republic of China; Department of Medical Oncology, The Affiliated Hospital of Medical College Qingdao University, Qingdao, People's Republic of China; Department of Gastrointestinal Medical Oncology, Peking University Cancer Hospital, Beijing, People's Republic of China; Department of Medical Oncology, Heilongjiang Province Cancer Hospital, Harbin, People's Republic of China; Medical Affairs, Sanofi China, Shanghai, People's Republic of China; Department of Hepatobiliary Surgery, Zhong Shan Hospital, Shanghai, People's Republic of China; Department of Hepatobiliary Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China; Department of Interventional Radiology, Sun Yat-sen University Cancer Hospital, Guangzhou, People's Republic of China; Department of Medical Oncology, Wuhan Union Hospital, Hubei, People's Republic of China; Department of Medical Oncology, Kaohsiung Chang-Gung Memorial Hospital, Kaohsiung, Taiwan, Republic of China; LinKou Medical Center, Chang-Gung Memorial Hospital, Taoyuan, Taiwan, Republic of China; Department of Hepatobiliary Surgery, Guangdong General Hospital, Guangzhou, People's Republic of China; Department of Medical Oncology, Southwest Hospital, Chongqing, People's Republic of China; Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing, People's Republic of China
| | - Jia Fan
- People's Liberation Army Cancer Center, Bayi Hospital, Nanjing, People's Republic of China; Department of Medical Oncology, Jilin Province Cancer Hospital, Changchun, People's Republic of China; Department of Medical Oncology, The Affiliated Hospital of Medical College Qingdao University, Qingdao, People's Republic of China; Department of Gastrointestinal Medical Oncology, Peking University Cancer Hospital, Beijing, People's Republic of China; Department of Medical Oncology, Heilongjiang Province Cancer Hospital, Harbin, People's Republic of China; Medical Affairs, Sanofi China, Shanghai, People's Republic of China; Department of Hepatobiliary Surgery, Zhong Shan Hospital, Shanghai, People's Republic of China; Department of Hepatobiliary Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China; Department of Interventional Radiology, Sun Yat-sen University Cancer Hospital, Guangzhou, People's Republic of China; Department of Medical Oncology, Wuhan Union Hospital, Hubei, People's Republic of China; Department of Medical Oncology, Kaohsiung Chang-Gung Memorial Hospital, Kaohsiung, Taiwan, Republic of China; LinKou Medical Center, Chang-Gung Memorial Hospital, Taoyuan, Taiwan, Republic of China; Department of Hepatobiliary Surgery, Guangdong General Hospital, Guangzhou, People's Republic of China; Department of Medical Oncology, Southwest Hospital, Chongqing, People's Republic of China; Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing, People's Republic of China
| | - Lijian Liang
- People's Liberation Army Cancer Center, Bayi Hospital, Nanjing, People's Republic of China; Department of Medical Oncology, Jilin Province Cancer Hospital, Changchun, People's Republic of China; Department of Medical Oncology, The Affiliated Hospital of Medical College Qingdao University, Qingdao, People's Republic of China; Department of Gastrointestinal Medical Oncology, Peking University Cancer Hospital, Beijing, People's Republic of China; Department of Medical Oncology, Heilongjiang Province Cancer Hospital, Harbin, People's Republic of China; Medical Affairs, Sanofi China, Shanghai, People's Republic of China; Department of Hepatobiliary Surgery, Zhong Shan Hospital, Shanghai, People's Republic of China; Department of Hepatobiliary Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China; Department of Interventional Radiology, Sun Yat-sen University Cancer Hospital, Guangzhou, People's Republic of China; Department of Medical Oncology, Wuhan Union Hospital, Hubei, People's Republic of China; Department of Medical Oncology, Kaohsiung Chang-Gung Memorial Hospital, Kaohsiung, Taiwan, Republic of China; LinKou Medical Center, Chang-Gung Memorial Hospital, Taoyuan, Taiwan, Republic of China; Department of Hepatobiliary Surgery, Guangdong General Hospital, Guangzhou, People's Republic of China; Department of Medical Oncology, Southwest Hospital, Chongqing, People's Republic of China; Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing, People's Republic of China
| | - Yaqi Zhang
- People's Liberation Army Cancer Center, Bayi Hospital, Nanjing, People's Republic of China; Department of Medical Oncology, Jilin Province Cancer Hospital, Changchun, People's Republic of China; Department of Medical Oncology, The Affiliated Hospital of Medical College Qingdao University, Qingdao, People's Republic of China; Department of Gastrointestinal Medical Oncology, Peking University Cancer Hospital, Beijing, People's Republic of China; Department of Medical Oncology, Heilongjiang Province Cancer Hospital, Harbin, People's Republic of China; Medical Affairs, Sanofi China, Shanghai, People's Republic of China; Department of Hepatobiliary Surgery, Zhong Shan Hospital, Shanghai, People's Republic of China; Department of Hepatobiliary Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China; Department of Interventional Radiology, Sun Yat-sen University Cancer Hospital, Guangzhou, People's Republic of China; Department of Medical Oncology, Wuhan Union Hospital, Hubei, People's Republic of China; Department of Medical Oncology, Kaohsiung Chang-Gung Memorial Hospital, Kaohsiung, Taiwan, Republic of China; LinKou Medical Center, Chang-Gung Memorial Hospital, Taoyuan, Taiwan, Republic of China; Department of Hepatobiliary Surgery, Guangdong General Hospital, Guangzhou, People's Republic of China; Department of Medical Oncology, Southwest Hospital, Chongqing, People's Republic of China; Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing, People's Republic of China
| | - Gang Wu
- People's Liberation Army Cancer Center, Bayi Hospital, Nanjing, People's Republic of China; Department of Medical Oncology, Jilin Province Cancer Hospital, Changchun, People's Republic of China; Department of Medical Oncology, The Affiliated Hospital of Medical College Qingdao University, Qingdao, People's Republic of China; Department of Gastrointestinal Medical Oncology, Peking University Cancer Hospital, Beijing, People's Republic of China; Department of Medical Oncology, Heilongjiang Province Cancer Hospital, Harbin, People's Republic of China; Medical Affairs, Sanofi China, Shanghai, People's Republic of China; Department of Hepatobiliary Surgery, Zhong Shan Hospital, Shanghai, People's Republic of China; Department of Hepatobiliary Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China; Department of Interventional Radiology, Sun Yat-sen University Cancer Hospital, Guangzhou, People's Republic of China; Department of Medical Oncology, Wuhan Union Hospital, Hubei, People's Republic of China; Department of Medical Oncology, Kaohsiung Chang-Gung Memorial Hospital, Kaohsiung, Taiwan, Republic of China; LinKou Medical Center, Chang-Gung Memorial Hospital, Taoyuan, Taiwan, Republic of China; Department of Hepatobiliary Surgery, Guangdong General Hospital, Guangzhou, People's Republic of China; Department of Medical Oncology, Southwest Hospital, Chongqing, People's Republic of China; Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing, People's Republic of China
| | - Kun-Ming Rau
- People's Liberation Army Cancer Center, Bayi Hospital, Nanjing, People's Republic of China; Department of Medical Oncology, Jilin Province Cancer Hospital, Changchun, People's Republic of China; Department of Medical Oncology, The Affiliated Hospital of Medical College Qingdao University, Qingdao, People's Republic of China; Department of Gastrointestinal Medical Oncology, Peking University Cancer Hospital, Beijing, People's Republic of China; Department of Medical Oncology, Heilongjiang Province Cancer Hospital, Harbin, People's Republic of China; Medical Affairs, Sanofi China, Shanghai, People's Republic of China; Department of Hepatobiliary Surgery, Zhong Shan Hospital, Shanghai, People's Republic of China; Department of Hepatobiliary Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China; Department of Interventional Radiology, Sun Yat-sen University Cancer Hospital, Guangzhou, People's Republic of China; Department of Medical Oncology, Wuhan Union Hospital, Hubei, People's Republic of China; Department of Medical Oncology, Kaohsiung Chang-Gung Memorial Hospital, Kaohsiung, Taiwan, Republic of China; LinKou Medical Center, Chang-Gung Memorial Hospital, Taoyuan, Taiwan, Republic of China; Department of Hepatobiliary Surgery, Guangdong General Hospital, Guangzhou, People's Republic of China; Department of Medical Oncology, Southwest Hospital, Chongqing, People's Republic of China; Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing, People's Republic of China
| | - Tsai-Shen Yang
- People's Liberation Army Cancer Center, Bayi Hospital, Nanjing, People's Republic of China; Department of Medical Oncology, Jilin Province Cancer Hospital, Changchun, People's Republic of China; Department of Medical Oncology, The Affiliated Hospital of Medical College Qingdao University, Qingdao, People's Republic of China; Department of Gastrointestinal Medical Oncology, Peking University Cancer Hospital, Beijing, People's Republic of China; Department of Medical Oncology, Heilongjiang Province Cancer Hospital, Harbin, People's Republic of China; Medical Affairs, Sanofi China, Shanghai, People's Republic of China; Department of Hepatobiliary Surgery, Zhong Shan Hospital, Shanghai, People's Republic of China; Department of Hepatobiliary Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China; Department of Interventional Radiology, Sun Yat-sen University Cancer Hospital, Guangzhou, People's Republic of China; Department of Medical Oncology, Wuhan Union Hospital, Hubei, People's Republic of China; Department of Medical Oncology, Kaohsiung Chang-Gung Memorial Hospital, Kaohsiung, Taiwan, Republic of China; LinKou Medical Center, Chang-Gung Memorial Hospital, Taoyuan, Taiwan, Republic of China; Department of Hepatobiliary Surgery, Guangdong General Hospital, Guangzhou, People's Republic of China; Department of Medical Oncology, Southwest Hospital, Chongqing, People's Republic of China; Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing, People's Republic of China
| | - Zhixiang Jian
- People's Liberation Army Cancer Center, Bayi Hospital, Nanjing, People's Republic of China; Department of Medical Oncology, Jilin Province Cancer Hospital, Changchun, People's Republic of China; Department of Medical Oncology, The Affiliated Hospital of Medical College Qingdao University, Qingdao, People's Republic of China; Department of Gastrointestinal Medical Oncology, Peking University Cancer Hospital, Beijing, People's Republic of China; Department of Medical Oncology, Heilongjiang Province Cancer Hospital, Harbin, People's Republic of China; Medical Affairs, Sanofi China, Shanghai, People's Republic of China; Department of Hepatobiliary Surgery, Zhong Shan Hospital, Shanghai, People's Republic of China; Department of Hepatobiliary Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China; Department of Interventional Radiology, Sun Yat-sen University Cancer Hospital, Guangzhou, People's Republic of China; Department of Medical Oncology, Wuhan Union Hospital, Hubei, People's Republic of China; Department of Medical Oncology, Kaohsiung Chang-Gung Memorial Hospital, Kaohsiung, Taiwan, Republic of China; LinKou Medical Center, Chang-Gung Memorial Hospital, Taoyuan, Taiwan, Republic of China; Department of Hepatobiliary Surgery, Guangdong General Hospital, Guangzhou, People's Republic of China; Department of Medical Oncology, Southwest Hospital, Chongqing, People's Republic of China; Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing, People's Republic of China
| | - Houjie Liang
- People's Liberation Army Cancer Center, Bayi Hospital, Nanjing, People's Republic of China; Department of Medical Oncology, Jilin Province Cancer Hospital, Changchun, People's Republic of China; Department of Medical Oncology, The Affiliated Hospital of Medical College Qingdao University, Qingdao, People's Republic of China; Department of Gastrointestinal Medical Oncology, Peking University Cancer Hospital, Beijing, People's Republic of China; Department of Medical Oncology, Heilongjiang Province Cancer Hospital, Harbin, People's Republic of China; Medical Affairs, Sanofi China, Shanghai, People's Republic of China; Department of Hepatobiliary Surgery, Zhong Shan Hospital, Shanghai, People's Republic of China; Department of Hepatobiliary Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China; Department of Interventional Radiology, Sun Yat-sen University Cancer Hospital, Guangzhou, People's Republic of China; Department of Medical Oncology, Wuhan Union Hospital, Hubei, People's Republic of China; Department of Medical Oncology, Kaohsiung Chang-Gung Memorial Hospital, Kaohsiung, Taiwan, Republic of China; LinKou Medical Center, Chang-Gung Memorial Hospital, Taoyuan, Taiwan, Republic of China; Department of Hepatobiliary Surgery, Guangdong General Hospital, Guangzhou, People's Republic of China; Department of Medical Oncology, Southwest Hospital, Chongqing, People's Republic of China; Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing, People's Republic of China
| | - Yan Sun
- People's Liberation Army Cancer Center, Bayi Hospital, Nanjing, People's Republic of China; Department of Medical Oncology, Jilin Province Cancer Hospital, Changchun, People's Republic of China; Department of Medical Oncology, The Affiliated Hospital of Medical College Qingdao University, Qingdao, People's Republic of China; Department of Gastrointestinal Medical Oncology, Peking University Cancer Hospital, Beijing, People's Republic of China; Department of Medical Oncology, Heilongjiang Province Cancer Hospital, Harbin, People's Republic of China; Medical Affairs, Sanofi China, Shanghai, People's Republic of China; Department of Hepatobiliary Surgery, Zhong Shan Hospital, Shanghai, People's Republic of China; Department of Hepatobiliary Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China; Department of Interventional Radiology, Sun Yat-sen University Cancer Hospital, Guangzhou, People's Republic of China; Department of Medical Oncology, Wuhan Union Hospital, Hubei, People's Republic of China; Department of Medical Oncology, Kaohsiung Chang-Gung Memorial Hospital, Kaohsiung, Taiwan, Republic of China; LinKou Medical Center, Chang-Gung Memorial Hospital, Taoyuan, Taiwan, Republic of China; Department of Hepatobiliary Surgery, Guangdong General Hospital, Guangzhou, People's Republic of China; Department of Medical Oncology, Southwest Hospital, Chongqing, People's Republic of China; Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing, People's Republic of China
| |
Collapse
|
|
27
|
Goldstein R, Yu D, Gillmore R, Thirlwell C, O'Donoghue P, Mayer A, Meyer T. Oxaliplatin/5-fluorouracil in advanced hepatocellular carcinoma: case report and single-center retrospective review. Future Oncol 2014; 10:2007-14. [PMID: 25209630 DOI: 10.2217/fon.14.108] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
AIMS Sorafenib is the only standard therapy for advanced hepatocellular carcinoma, but has a low response rate. Leucovorin and oxaliplatin (FOLFOX) has a superior response rate versus doxorubicin among Asian sorafenib-naive patients. We aimed to retrospectively review the outcome of 20 consecutive patients treated with FOLFOX at a single European center. MATERIALS & METHODS Patients had symptomatic disease burdens unlikely to regress with sorafenib or had no proven treatment options (sorafenib-refractory or recurrence post liver transplantation). RESULTS One sorafenib-refractory patient had a complete response and two liver transplant patients experienced partial responses. Median overall survival was 6.3 months. There was one chemotherapy death due to neutropenic sepsis. CONCLUSION In advanced hepatocellular carcinoma, FOLFOX can induce clinically relevant responses, but needs prospective validation.
Collapse
Affiliation(s)
- Robert Goldstein
- UCL Cancer Institute, University College London, Gower Street, London, WC1E 6BT, UK
| | | | | | | | | | | | | |
Collapse
|
|
28
|
Forner A, Gilabert M, Bruix J, Raoul JL. Treatment of intermediate-stage hepatocellular carcinoma. Nat Rev Clin Oncol 2014; 11:525-35. [PMID: 25091611 DOI: 10.1038/nrclinonc.2014.122] [Citation(s) in RCA: 343] [Impact Index Per Article: 31.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Hepatocellular carcinoma (HCC)-closely associated with liver cirrhosis and, in fact, the main cause of death in patients with such disease-is now recognized as one of the most-prevalent and lethal neoplasms worldwide. Prognosis and allocation of the multiple available treatment options for patients with HCC are influenced not only by tumour stage, but also by the degree of liver-function impairment. Therefore, accurate assessment and classification of disease is important for patient management. According to the Barcelona Clinic Liver Cancer (BCLC) algorithm, intermediate-stage HCC is defined as extensive multifocal disease without vascular invasion in patients with preserved liver function and absence of cancer-related symptoms; in this context, transarterial chemoembolization (TACE) is considered the standard treatment. The use of drug-eluting beads has enabled standardization of this procedure, resulting in higher reproducibility and tolerability of the treatment. Nevertheless, not all patients with intermediate-stage HCC are good candidates for TACE and, for such patients in whom TACE is not appropriate or has failed, other treatments can be considered, including sorafenib. Radioembolization is a promising alternative that deserves further prospective studies. Herein, we review the current approaches used to accurately stratify patients with intermediate-stage HCC and subsequently allocate the most-appropriate treatments. The key developments in therapeutic strategies are also discussed.
Collapse
Affiliation(s)
- Alejandro Forner
- Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Centre for Biomedical Research Network for Hepatic and Digestive Diseases, Hospital Clinic Barcelona, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), University of Barcelona, C/ Villarroel 170, 08036 Barcelona, Spain
| | - Marine Gilabert
- Department of Medical Oncology, Institut Paoli-Calmettes, 232 Boulevard de Sainte Marguerite, 13009 Marseille, France
| | - Jordi Bruix
- Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Centre for Biomedical Research Network for Hepatic and Digestive Diseases, Hospital Clinic Barcelona, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), University of Barcelona, C/ Villarroel 170, 08036 Barcelona, Spain
| | - Jean-Luc Raoul
- Department of Medical Oncology, Institut Paoli-Calmettes, 232 Boulevard de Sainte Marguerite, 13009 Marseille, France
| |
Collapse
|
|
29
|
Forner A, Gilabert M, Bruix J, Raoul JL. Treatment of intermediate-stage hepatocellular carcinoma. Nat Rev Clin Oncol 2014. [PMID: 25091611 DOI: 10.1038/nrclinonc.2014] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Hepatocellular carcinoma (HCC)-closely associated with liver cirrhosis and, in fact, the main cause of death in patients with such disease-is now recognized as one of the most-prevalent and lethal neoplasms worldwide. Prognosis and allocation of the multiple available treatment options for patients with HCC are influenced not only by tumour stage, but also by the degree of liver-function impairment. Therefore, accurate assessment and classification of disease is important for patient management. According to the Barcelona Clinic Liver Cancer (BCLC) algorithm, intermediate-stage HCC is defined as extensive multifocal disease without vascular invasion in patients with preserved liver function and absence of cancer-related symptoms; in this context, transarterial chemoembolization (TACE) is considered the standard treatment. The use of drug-eluting beads has enabled standardization of this procedure, resulting in higher reproducibility and tolerability of the treatment. Nevertheless, not all patients with intermediate-stage HCC are good candidates for TACE and, for such patients in whom TACE is not appropriate or has failed, other treatments can be considered, including sorafenib. Radioembolization is a promising alternative that deserves further prospective studies. Herein, we review the current approaches used to accurately stratify patients with intermediate-stage HCC and subsequently allocate the most-appropriate treatments. The key developments in therapeutic strategies are also discussed.
Collapse
Affiliation(s)
- Alejandro Forner
- Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Centre for Biomedical Research Network for Hepatic and Digestive Diseases, Hospital Clinic Barcelona, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), University of Barcelona, C/ Villarroel 170, 08036 Barcelona, Spain
| | - Marine Gilabert
- Department of Medical Oncology, Institut Paoli-Calmettes, 232 Boulevard de Sainte Marguerite, 13009 Marseille, France
| | - Jordi Bruix
- Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Centre for Biomedical Research Network for Hepatic and Digestive Diseases, Hospital Clinic Barcelona, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), University of Barcelona, C/ Villarroel 170, 08036 Barcelona, Spain
| | - Jean-Luc Raoul
- Department of Medical Oncology, Institut Paoli-Calmettes, 232 Boulevard de Sainte Marguerite, 13009 Marseille, France
| |
Collapse
|
|
30
|
|
|
31
|
Oxaliplatin-based chemotherapy: a new option in advanced hepatocellular carcinoma. a systematic review and pooled analysis. Clin Oncol (R Coll Radiol) 2014; 26:488-96. [PMID: 24856442 DOI: 10.1016/j.clon.2014.04.031] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2013] [Revised: 02/17/2014] [Accepted: 03/18/2014] [Indexed: 12/13/2022]
Abstract
Advanced hepatocellular carcinoma (HCC), for which locoregional treatment is not an option, is a candidate for palliative systemic therapy, but an accepted chemotherapy regimen does not exist. We have conducted a systematic literature review and meta-analyses to quantify the benefits of oxaliplatin (OXA)-based chemotherapy in advanced HCC in patients not exposed to sorafenib. Studies that enrolled advanced HCC patients treated with first-line OXA-based chemotherapy were identified using PubMed, Web of Science, SCOPUS, The Cochrane Register of Controlled Trials and EMBASE. A systematic review was conducted to calculate the pooled response rate and 95% confidence interval. The pooled median progression-free survival (PFS) and overall survival, weighted on the number of patients of each selected trials, were also calculated. We tested for significant heterogeneity by Cochran's chi-squared test and I-square index. Thirteen studies were included in this review, with a total of 800 patients analysed. The pooled response rate was 16.8%. The median PFS and overall survival were 4.2 and 9.3 months, respectively, with a 1 year overall survival of 37%. The weighted median PFS/overall survival and response rate were 4.5/11 months and 20% in Western patients. Conversely, in Asiatic studies, the median PFS/overall survival and response rate were 2.43/6.47 months and 13.2%, respectively. OXA-based chemotherapy is effective in advanced HCC and represents a viable option in these patients. A head to head comparison with sorafenib or a second-line agent should be verified in prospective trials.
Collapse
|
|
32
|
Ogasawara S, Chiba T, Ooka Y, Kanogawa N, Motoyama T, Suzuki E, Tawada A, Kanai F, Yokosuka AO. A phase I/II trial of capecitabine combined with peginterferon α-2a in Patients with sorafenib-refractory advanced hepatocellular carcinoma. Invest New Drugs 2014; 32:762-8. [PMID: 24737402 DOI: 10.1007/s10637-014-0097-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2014] [Accepted: 03/30/2014] [Indexed: 12/17/2022]
Abstract
BACKGROUND Several pilot studies have demonstrated the effectiveness of combination therapy with pyrimidine fluoride and interferon for advanced hepatocellular carcinoma.This study aimed to determine the recommended dose of capecitabine combined with peginterferon α-2a (Phase I) and evaluate its safety and efficacy for sorafenib-refractory advanced hepatocellular carcinoma (Phase II). METHODS Capecitabine was administered daily on days 1-14, while peginterferon α-2a was administered on days 1, 8, and 15. The cycle was repeated every 21 days. The patients were scheduled to receive capecitabine [mg/(m(2)∙day)] and peginterferon α-2a (μg/week) at 3 dose levels in phase I: 1200 and 90 (level 1), 1600 and 90 (level 2), and 2000 and 90 (level 3), respectively. RESULTS A total of 30 patients were enrolled. The recommended dose was level 3. Among the 24 patients receiving the drug at the recommended dosage, 2 (8 %) exhibited a partial response, 9 (38 %) exhibited stable disease, 10 (42 %) exhibited progressive disease, and 3 (13 %) were not evaluated. The median time to progression and overall survival were 3.0 months and 7.2 months, respectively. The most common toxicities were decreased white blood cell (88 %), neutrophil (88 %), and platelet counts (58 %); fatigue (50 %); and palmar-plantar erythrodysesthesia syndrome (42 %). Four patients (17 %) discontinued treatment because of severe adverse events. CONCLUSION Capecitabine at 2000 mg/(m(2)∙day) combined with peginterferon α-2a (90 μg/week) exhibited moderate, albeit manageable, toxicity and was declared as the recommended phase II dose. Further research is required to refine the efficacy of this combination.
Collapse
Affiliation(s)
- Sadahisa Ogasawara
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan
| | | | | | | | | | | | | | | | | |
Collapse
|
|
33
|
Bevacizumab and erlotinib in previously untreated inoperable and metastatic hepatocellular carcinoma. Am J Clin Oncol 2013; 36:254-7. [PMID: 22643560 DOI: 10.1097/coc.0b013e318248d83f] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
PURPOSE To evaluate the combination of erlotinib and bevacizumab in subjects with hepatocellular carcinoma (HCC) who are not candidates for local therapy. PATIENTS AND METHODS Twenty-one subjects with metastatic or inoperable HCC who had not received local or systemic therapy were treated with 15 mg/kg bevacizumab every 3 weeks and a daily dose of 150 mg oral erlotinib. The primary endpoint was progression-free survival (PFS) at 27 weeks. The secondary endpoints were median time to progression and median overall survival. RESULTS Twenty-one subjects were enrolled. Eighteen were evaluable for the primary endpoint; all subjects were evaluable for toxicity. The median age was 60 years (range, 33 to 81 y). Five subjects (28%) were progression free at 27 weeks (90% confidence interval (CI), 12%-50%). Median time to progression was 2.57 months (95% CI, 2.13-4.20 mo). Median overall survival was 8.33 months (95% CI, 5.73-13.97 mo). Two subjects withdrew consent, and 1 subject did not have adequate baseline scans. CONCLUSIONS The 28% progression-free survival rate at 27 weeks was not significantly higher than the recent historical control rate of 20% observed on the placebo arm of the Sorafenib Hepatocellular Carcinoma Assessment Randomized Protocol trial (P=0.28). The combination of bevacizumab and erlotinib does not appear to have sufficient efficacy in patients with unresectable and metastatic HCC not amenable to local therapy, and may not warrant further investigation. However, this could be evaluated as an alternative to those intolerant to sorafenib therapy.
Collapse
|
|
34
|
Verslype C, Rosmorduc O, Rougier P. Hepatocellular carcinoma: ESMO-ESDO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2013; 23 Suppl 7:vii41-8. [PMID: 22997453 DOI: 10.1093/annonc/mds225] [Citation(s) in RCA: 273] [Impact Index Per Article: 22.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Affiliation(s)
- C Verslype
- Department of Hepatology, University Hospitals Leuven, Leuven, Belgium
| | | | | | | |
Collapse
|
|
35
|
Yang J, Yan L, Wang W. Current status of multimodal & combination therapy for hepatocellular carcinoma. Indian J Med Res 2012; 136:391-403. [PMID: 23041732 PMCID: PMC3510885] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/03/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world. Surgery offers the only hope for cure. However, the potentially curable method is only possible for a small proportion of those afflicted, for the rest, palliative treatment is indicated. Despite all the treatment options when used as monotherapy, patients with HCC have a poor long term prognosis. In this setting, multimodal and combination therapy has emerged as an alternative treatment modality for HCC. Studies have looked at various forms of combination therapy, including neoadjuvant/adjuvant/downstaging therapy for surgery and the combined modality of non-operative therapies. The novel molecular targeted therapies are also being used as combination regimens for surgery or other non-operative therapies. Some forms of combination therapies, including downstaging therapy for surgery, salvage transplantation, and molecular targeted therapy have been shown to provide survival benefits for well selected patients, and need to be encouraged in the future. And others such as pre-operative bridging therapy for liver transplantation, adjuvant therapy for hepatic resection and combination of local and regional therapies have also shown some benefits in preliminary results, which need confirmation in further studies. In conclusion, multimodal and combination therapy is an encouraging treatment modality for HCC. Future research should continue to unravel the role of combination therapy with properly selected patients and appropriate end points.
Collapse
Affiliation(s)
- Jian Yang
- Division of Liver Transplantation, West China Hospital, West China Medical School of Sichuan University, Chengdu, PR China
| | - Lunan Yan
- Division of Liver Transplantation, West China Hospital, West China Medical School of Sichuan University, Chengdu, PR China,Reprint requests: Dr Lunan Yan, Division of Liver Transplantation, West China Hospital, West China School of Medicine, Sichuan University, 37# Guoxue Lane, Chengdu 610041, PR China e-mail:
| | - Wentao Wang
- Division of Liver Transplantation, West China Hospital, West China Medical School of Sichuan University, Chengdu, PR China
| |
Collapse
|
|
36
|
Azmy AM, Nasr KE, Gobran NS, Yassin M. Gemcitabine Plus Carboplatin in Patients with Advanced Hepatocellular Carcinoma: Results of a Phase II Study. ISRN ONCOLOGY 2012; 2012:420931. [PMID: 22848843 PMCID: PMC3405685 DOI: 10.5402/2012/420931] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/12/2012] [Accepted: 05/10/2012] [Indexed: 11/23/2022]
Abstract
Objectives. Assessment of gemcitabine/carboplatin combination in patients with advanced-stage hepatocellular carcinoma (HCC) in a phase II trial for safety and efficacy. Methods. Forty patients with previously untreated advanced-stage HCC were prospectively enrolled and subjected to gemcitabine/carboplatin regimen which consisted of gemcitabine 1000 mg/m2 on days 1 and 8, and carboplatin AUC 6 on day 1. The treatment was repeated every 3 weeks until disease progression or limiting toxicity. Results. Forty patients were assessable for efficacy and toxicity. In all, 276 treatment cycles were administered. No toxic deaths occurred. Hematological grade 3-4 toxicity consisted of thrombocytopenia (27% of patients) and neutropenia (24%), including 2 febrile neutropenia and anemia (9%). Grade 3 carboplatin-induced neurotoxicity was observed in 3 (9%) patients. ORR was 23% (95% CI, 0.10–0.29) with 9 partial responses and disease stabilization was observed in 46% (95% CI, 0.22–0.42) of patients, giving a disease control rate of 69%. Median progression-free and overall survival times were, respectively, 5 months (95% CI: 3–8 months) and 8 months (95% CI: 6–18 months). Conclusion. The gemcitabine/carboplatin regimen seems to be effective, well tolerated, and active in advanced HCC.
Collapse
Affiliation(s)
- Aly M Azmy
- Clinical Oncology Departement, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | | | | | | |
Collapse
|
|
37
|
Activity of Thalidomide and Capecitabine in Patients With Advanced Hepatocellular Carcinoma. Am J Clin Oncol 2012; 35:222-7. [DOI: 10.1097/coc.0b013e31820dbf56] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
|
|
38
|
Kim HR, Cheon SH, Rha SY, Lee S, Han KH, Chon CY, Lee JD, Sung JS, Chung HC. Treatment of recurrent hepatocellular carcinoma after liver transplantation. Asia Pac J Clin Oncol 2012; 7:258-69. [PMID: 21884437 DOI: 10.1111/j.1743-7563.2011.01425.x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
AIM Liver transplantation (LT) is a curative treatment for localized hepatocellular carcinoma (HCC), but the recurrence rate after LT is about 10-20%, with a dismal prognosis. Little data exist as to the natural history, treatment outcome and optimal treatment of recurrent HCC after LT. We reviewed various treatment modalities given to patients with recurrent HCC after LT. METHODS Among 132 patients who underwent LT for localized HCC, we retrospectively reviewed medical records of 39 of the 132 patients who developed recurrent HCC after LT. We analyzed the clinical outcome of various treatment modalities and treatment-related adverse events. RESULTS A total of 39 (29%) of the original 132 patients had recurrent HCC, most recurrences (82%) having occurred within 1 year after LT and involved extrahepatic lesions. Only seven patients had recurrent disease limited to the liver. The median overall survival from the initial treatment of all relapsed patients was 6.9 months. There were various initial treatment modalities, namely palliative systemic chemotherapy, trans-catheter arterial chemo-embolization/infusion (TACE/I), radiation therapy (RT), surgical resection and no treatment. The median overall survival was 9.5 months for first-line chemotherapy, including those who had prior local therapy, 6.3 months TACE/I and 6.9 months for RT. CONCLUSION Various clinical approaches have been used to treat patients with recurrent HCC after LT in a clinical setting. More effective strategies and clinical guidelines for recurrent HCC following LT must be established.
Collapse
Affiliation(s)
- Hye Ryun Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | | | | | | | | | | | | | | | | |
Collapse
|
|
39
|
Asghar U, Meyer T. Are there opportunities for chemotherapy in the treatment of hepatocellular cancer? J Hepatol 2012; 56:686-95. [PMID: 21971559 DOI: 10.1016/j.jhep.2011.07.031] [Citation(s) in RCA: 152] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2010] [Revised: 07/25/2011] [Accepted: 07/28/2011] [Indexed: 02/07/2023]
Abstract
Hepatocellular cancer is a significant global health problem yet the prognosis for the majority of patients has not changed significantly over the past few decades. For patients with advanced disease, sorafenib is currently the standard of care providing a survival advantage of 2-3 months in selected patients. Cytotoxic chemotherapy has been used for over 30 years but definite evidence that it prolongs survival has been lacking. Resistance remains a significant barrier for both targeted and cytotoxic agents and an understanding of the underlying mechanisms is critical if outcomes are to be improved. Here, we summarise the past and current data that constitute the evidence base for chemotherapy in HCC, review the causes of chemoresistance and suggest strategies to overcome these barriers.
Collapse
Affiliation(s)
- Uzma Asghar
- Department of Oncology, UCL Medical School, Royal Free Campus, London, UK
| | | |
Collapse
|
|
40
|
Cabibbo G, Palmeri L, Palmeri S, Craxì A. Should cirrhosis change our attitude towards treating non-hepatic cancer? Liver Int 2012; 32:21-7. [PMID: 22098398 DOI: 10.1111/j.1478-3231.2011.02629.x] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2010] [Accepted: 07/28/2011] [Indexed: 12/17/2022]
Abstract
Cirrhosis is a major cause of morbidity and mortality and is the end stage of any chronic liver disease. Cancer, a leading cause of death worldwide, is a growing global health issue. There are limited data in the literature on the incidence, prevalence and management of non-hepatic cancers (NHC) in cirrhotic patients. The aim of this brief review was to underline the main concerns, pitfalls and warnings regarding practice for these patients. Survival of patients with compensated cirrhosis is significantly longer than that of decompensated cirrhosis and patients with NHC and in Child-Pugh class C should not be candidates for cytotoxic chemotherapy. It is important before starting cytotoxic chemotherapy to assess the aetiology and stage of liver disease and to screen these patients for portal hypertension and fluid retention. During cytotoxic chemotherapy, the effectiveness of cancer treatment, as well the appearance of early signs of hepatic decompensation, must be thoroughly monitored. Future phase 3 trial designs in oncology should include a share of patients with compensated cirrhosis to obtain specific information in this setting. Identification of tests able to measure the global degree of hepatic impairment caused by cirrhosis could help in the management of this particular clinical situation.
Collapse
Affiliation(s)
- Giuseppe Cabibbo
- Sezione di Gastroenterologia, DIBIMIS, University of Palermo, Palermo, Italy.
| | | | | | | |
Collapse
|
|
41
|
Chen SW, Wang S, Wang B, Li WD, Yan S, Xie LP. Metachronous pulmonary and adrenal metastases after liver transplantation for hepatocarcinoma. World J Surg Oncol 2011; 9:156. [PMID: 22123282 PMCID: PMC3286431 DOI: 10.1186/1477-7819-9-156] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2011] [Accepted: 11/28/2011] [Indexed: 12/17/2022] Open
Abstract
Background The worldwide experience of surgical resection for isolated metastasis following liver transplantation (LT) for hepatocellular carcinoma (HCC) is limited. Methods The case of a 60-year-old patient performed successful surgical management for metachronous pulmonary and adrenal metastases from HCC after LT. Results Eighty months after LT, he was presently alive and disease-free with a normal AFP value. Conclusion The case is an interesting report on a somehow indolent metastatic spread of HCC after LT. It should be considered that metachronous metastatic resectable disease, with no data of recurrence at the primary site in an operable patient, is an indication to perform a surgical resection.
Collapse
Affiliation(s)
- Shan-Wen Chen
- Department of Urology, First Affiliated Hospital, Medical College of Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang, P.R. China.
| | | | | | | | | | | |
Collapse
|
|
42
|
Treatment of advanced hepatocellular carcinoma with very low levels of amplitude-modulated electromagnetic fields. Br J Cancer 2011; 105:640-8. [PMID: 21829195 PMCID: PMC3188936 DOI: 10.1038/bjc.2011.292] [Citation(s) in RCA: 59] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Background: Therapeutic options for patients with advanced hepatocellular carcinoma (HCC) are limited. There is emerging evidence that the growth of cancer cells may be altered by very low levels of electromagnetic fields modulated at specific frequencies. Methods: A single-group, open-label, phase I/II study was performed to assess the safety and effectiveness of the intrabuccal administration of very low levels of electromagnetic fields amplitude modulated at HCC-specific frequencies in 41 patients with advanced HCC and limited therapeutic options. Three-daily 60-min outpatient treatments were administered until disease progression or death. Imaging studies were performed every 8 weeks. The primary efficacy end point was progression-free survival ⩾6 months. Secondary efficacy end points were progression-free survival and overall survival. Results: Treatment was well tolerated and there were no NCI grade 2, 3 or 4 toxicities. In all, 14 patients (34.1%) had stable disease for more than 6 months. Median progression-free survival was 4.4 months (95% CI 2.1–5.3) and median overall survival was 6.7 months (95% CI 3.0–10.2). There were three partial and one near complete responses. Conclusion: Treatment with intrabuccally administered amplitude-modulated electromagnetic fields is safe, well tolerated, and shows evidence of antitumour effects in patients with advanced HCC.
Collapse
|
|
43
|
Abstract
Hepatocellular carcinoma (HCC) is an aggressive malignancy of the liver and occurs most often in the setting of chronic liver disease. The most common acquired causes for this are chronic viral hepatitis infections (mostly HBV and HCV), and alcohol. Other causes include nonalcoholic fatty liver disease-related nonalcoholic steatohepatitis, autoimmune liver disease, and biliary diseases. In addition, certain heritable diseases like hemochromatosis and α-1-antitrypsin deficiency can also lead to HCC. Therefore, prevention of HCC can be achieved by preventing and controlling these problems. For treatment, curative modalities are surgical resection and liver transplantation. However, most patients are not candidates for these surgical maneuvers, and outcomes are poor. New therapeutic developments have brought some improvement with both local and systemic disease control.
Collapse
Affiliation(s)
- Davendra P S Sohal
- Department of Medicine, Hematology and Oncology, Abramson Cancer Center, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104-4283, USA.
| | | |
Collapse
|
|
44
|
Wrzesinski SH, Taddei TH, Strazzabosco M. Systemic therapy in hepatocellular carcinoma. Clin Liver Dis 2011; 15:423-41, vii-x. [PMID: 21689622 PMCID: PMC3758582 DOI: 10.1016/j.cld.2011.03.002] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Many potential systemic therapies are being investigated for the treatment of hepatocellular carcinoma (HCC). The incidence of this malignancy is rising sharply and the vast majority of patients present at advanced stages. Although the earlier dismal results with cytotoxic chemotherapies made way for the development of locoregional therapies that provided improved overall survival, truly personalized therapy will require the selection of phenotypically similar stages of disease and populations, an understanding of the complex molecular and genetic pathways leading to HCC, and a keen understanding of the pathobiology of cirrhosis. Only then will we understand how to offer a particular patient at a specific stage of disease the appropriate therapy to truly prolong survival.
Collapse
Affiliation(s)
- Stephen H. Wrzesinski
- Yale Comprehensive Cancer Center, Yale University School of Medicine, New Haven, CT, USA,VA Connecticut Healthcare System, Comprehensive Cancer Center, 950 Campbell Avenue–111D, West Haven, CT 06516–2700, USA
| | - Tamar H. Taddei
- Department of Internal Medicine, Section of Digestive Diseases, Yale University School of Medicine, 333 Cedar Street/1080 LMP, PO Box 208019, New Haven, CT 06520–8019, USA,VA Connecticut Healthcare System, Hepatitis C Resource Center (HCRC), 950 Campbell Avenue-111H, West Haven, CT 06516-2700, USA
| | - Mario Strazzabosco
- Department of Internal Medicine, Section of Digestive Diseases, Yale University School of Medicine, 333 Cedar Street/1080 LMP, PO Box 208019, New Haven, CT 06520–8019, USA,Yale Liver Center, Department of Internal Medicine, Yale University, Cedar Street 333, New Haven, CT 06520, USA,Section of Digestive Diseases, University of Milan-Bicocca, Monza, Italy,Corresponding author. Department of Internal Medicine, Section of Digestive Diseases, Yale University School of Medicine, 333 Cedar Street/1080 LMP, PO Box 208019, New Haven, CT 06520-8019.
| |
Collapse
|
|
45
|
Sanoff HK, Bernard S, Goldberg RM, Morse MA, Garcia R, Woods L, Moore DT, O'Neil BH. Phase II Study of Capecitabine, Oxaliplatin, and Cetuximab for Advanced Hepatocellular Carcinoma. GASTROINTESTINAL CANCER RESEARCH : GCR 2011; 4:78-83. [PMID: 22043322 PMCID: PMC3201640] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Subscribe] [Scholar Register] [Received: 10/01/2009] [Accepted: 03/16/2010] [Indexed: 05/31/2023]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is frequently resistant to chemotherapy. However, epidermal growth factor receptor (EGFR) inhibition has demonstrated activity in HCC and overcomes chemotherapy resistance in other settings. We studied the efficacy of combining the anti-EGFR antibody cetuximab with capecitabine and oxaliplatin in advanced HCC. METHODS Patients who had chemotherapy-naive advanced/unresectable HCC and any Childs-Pugh-class chronic liver disease (provided bilirubin was <3 mg/dl) received capecitabine 850 mg/m(2) bid days 1-14, oxaliplatin 130 mg/m(2) day 1, and cetuximab 400 mg/m(2) day 1 then 250 mg/m(2) weekly for each 21 day cycle. RESULTS Twenty-nine patients received any protocol therapy, but 24 completed at least one cycle. Of the 24 patients evaluable for response, 3 had a partial response (12.5%, 95% confidence interval [CI], 3-32%) and 17 had stable disease (71%), for a disease control rate of 83%. Of patients with an elevated AFP, 57% had a >50% reduction in AFP. Median time to progression was 4.5 months (95% CI, 3.2-6.4), and overall survival was 4.4 months (95% CI, 2.4-7.3). Most common toxicities included diarrhea (13 patients, 45%), fatigue (12 patients, 41%), and hypomagnesemia (12 patients, 41%). Fatigue (6 patients) and diarrhea (5 patients) were the most common grade 3-4 toxicities. Three patients died within the first 30 days of treatment (one of toxicity, two of liver failure presumed to be related to disease progression). CONCLUSIONS The capecitabine/oxaliplatin/cetuximab combination was tolerable, though diarrhea was pronounced, in this population. The combination was associated with a modest response rate, but a high rate of AFP response and radiographic stable disease. Time to progression and overall survival were shorter than would be expected for treatment with sorafenib.
Collapse
|
|
46
|
Sun W, Sohal D, Haller DG, Mykulowycz K, Rosen M, Soulen MC, Caparro M, Teitelbaum UR, Giantonio B, O'Dwyer PJ, Shaked A, Reddy R, Olthoff K. Phase 2 trial of bevacizumab, capecitabine, and oxaliplatin in treatment of advanced hepatocellular carcinoma. Cancer 2011; 117:3187-92. [PMID: 21264839 DOI: 10.1002/cncr.25889] [Citation(s) in RCA: 73] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2010] [Revised: 11/18/2010] [Accepted: 11/29/2010] [Indexed: 12/12/2022]
Abstract
BACKGROUND Anti-angiogenesis agents have shown effectiveness in treatment of hepatocellular carcinoma (HCC). It is important to investigate more effective and safe systemic treatment options for patients with advanced HCC. This phase 2 study was designed to determine the efficacy and toxicity of the combination of bevacizumab, capecitabine, and oxaliplatin in patients with advanced unresectable and untransplantable HCC. METHODS Chemotherapy-naive patients with advanced unresectable and untransplantable HCC were treated with bevacizumab 5 mg/kg and oxaliplatin 130 mg/m(2) on day 1 of each cycle, and capecitabine 825 mg/m² orally twice a day from days 1 to 14 of a 21-day cycle. RESULTS Forty patients were enrolled to the study, in which 40% had Child-Pugh B disease. Forty percent had an Eastern Cooperative Oncology Group performance status (PS) of 0, 55% had PS of 1, and 5% had PS of 2. Forty percent of patients had hepatitis B virus infection. The median progression-free survival was 6.8 months (95% CI, 3.4-9.1 months), and the median overall survival was 9.8 months (95% CI, 5.2-12.1 months). Eight patients (20%) achieved partial response; 23 patients had stable disease with overall 77.5% disease control rate. The combination was tolerable with limited grade 3/4 toxicity, mainly peripheral neurotoxicity and fatigue. CONCLUSIONS The combination appeared effective and safe, and the results were encouraging. Further investigation should be considered.
Collapse
Affiliation(s)
- Weijing Sun
- Abramson Cancer Center, Department of Medicine, Hematology-Oncology Division, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
| | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
47
|
Wu Q, Qin SK, Teng FM, Chen CJ, Wang R. Lobaplatin arrests cell cycle progression in human hepatocellular carcinoma cells. J Hematol Oncol 2010; 3:43. [PMID: 21034513 PMCID: PMC2988698 DOI: 10.1186/1756-8722-3-43] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2010] [Accepted: 10/31/2010] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) still is a big burden for China. In recent years, the third-generation platinum compounds have been proposed as potential active agents for HCC. However, more experimental and clinical data are warranted to support the proposal. In the present study, the effect of lobaplatin was assessed in five HCC cell lines and the underlying molecular mechanisms in terms of cell cycle kinetics were explored. METHODS Cytotoxicity of lobaplatin to human HCC cell lines was examined using MTT cell proliferation assay. Cell cycle distribution was determined by flow cytometry. Expression of cell cycle-regulated genes was examined at both the mRNA (RT-PCR) and protein (Western blot) levels. The phosphorylation status of cyclin-dependent kinases (CDKs) and retinoblastoma (Rb) protein was also examined using Western blot analysis. RESULTS Lobaplatin inhibited proliferation of human HCC cells in a dose-dependent manner. For the most sensitive SMMC-7721 cells, lobaplatin arrested cell cycle progression in G1 and G2/M phases time-dependently which might be associated with the down-regulation of cyclin B, CDK1, CDC25C, phosphorylated CDK1 (pCDK1), pCDK4, Rb, E2F, and pRb, and the up-regulation of p53, p21, and p27. CONCLUSION Cytotoxicity of lobaplatin in human HCC cells might be due to its ability to arrest cell cycle progression which would contribute to the potential use of lobaplatin for the management of HCC.
Collapse
Affiliation(s)
- Qiong Wu
- Department of Medical Oncology, Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China
| | | | | | | | | |
Collapse
|
|
48
|
Traitements du carcinome hépatocellulaire non accessible à un traitement curatif: actualités. ONCOLOGIE 2010. [DOI: 10.1007/s10269-010-1945-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
|
|
49
|
Xia Y, Qiu Y, Li J, Shi L, Wang K, Xi T, Shen F, Yan Z, Wu M. Adjuvant therapy with capecitabine postpones recurrence of hepatocellular carcinoma after curative resection: a randomized controlled trial. Ann Surg Oncol 2010; 17:3137-44. [PMID: 20602260 DOI: 10.1245/s10434-010-1148-3] [Citation(s) in RCA: 61] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2009] [Indexed: 02/06/2023]
Abstract
BACKGROUND Postoperative recurrence of hepatocellular carcinoma (HCC) is a major problem after surgical resection. To date, adjuvant chemotherapy or other adjuvant modalities have not been proven effective in preventing or delaying recurrence. The aim of this prospective randomized study was to evaluate the effectiveness of capecitabine as a postoperative adjuvant regimen in inhibiting the recurrence of HCC. MATERIALS AND METHODS Between August 2003 and January 2005, 60 HCC patients who underwent curative resection were randomized into a capecitabine (n = 30) or a control (n = 30) group. The capecitabine group received 4-6 episodes of capecitabine treatment plus routine supportive care. Each episode consisted of 2 weeks of capecitabine followed by 1-week rest. The control group received routine supportive care only. The follow-up was 4-65 months (median: 47.5 months). RESULTS Cancer recurred in 16 patients (53.3%) in the capecitabine group and in 23 patients (76.7%) in the control group. The median time to recurrence (TTR) was 40.0 months (95% confidence interval [95% CI], 31.0-49.2 months) and 20.0 months (95% CI, 12.8-27.2 months) in the capecitabine and control groups, respectively (P = 0.046). The 5-year overall survival rate was 62.5% and 39.8% in the capecitabine group and control group, respectively (P = .216). Adverse reactions to capecitabine were generally mild and included nausea, vomiting, diarrhea, and decreased white blood cell and/or platelet counts. CONCLUSION Postoperative adjuvant therapy with capecitabine is well tolerated, postpones the recurrence of HCC, and reduces the risk of tumor recurrence. In addition, it is likely to improve postoperative survival.
Collapse
Affiliation(s)
- Yong Xia
- The First Department of Comprehensive Treatment, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | | | | | | | | | | | | | | | | |
Collapse
|
|
50
|
Whang-Peng J, Cheng AL, Hsu C, Chen CM. Clinical Development and Future Direction for the Treatment of Hepatocellular Carcinoma. ACTA ACUST UNITED AC 2010. [DOI: 10.1016/s1878-3317(10)60016-2] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
|